Renal protective effect of Cinnamon ethanolic extract against induced renal damage by carbon tetrachloride administration in rats

doi:10.21203/rs.3.rs-1425027/v1

Download PDF

Research Article

Renal protective effect of Cinnamon ethanolic extract against induced renal damage by carbon tetrachloride administration in rats

https://doi.org/10.21203/rs.3.rs-1425027/v1

This work is licensed under a CC BY 4.0 License

Version 1

posted

You are reading this latest preprint version

One of the most dangerous environmental contaminants is carbon tetrachloride (CCl4) that induces oxidative stress damage in various pathophysiological situations. It's critical to find a potent antioxidant that can reverse CCl4-induced kidney damage. Therefore, the aim of this study was to investigate the efficacy of cinnamon ethanolic extract (CE) to modulate the kidney damage induced by CCl4. The CCl4 was given intraperitoneally twice a week for four weeks as a positive kidney toxic agent at a dose of 0.5 mL/kg. Compared to normal group, CCl4 increased significantly MDA level and decreased significantly both SOD and GSH levels whereas, CE significantly decreased MDA level and increased both SOD as well as GSH levels relative to CCl4 group. CCl4 also led to increase in tumor necrosis factor alpha (TNF-α), beta-2 microglobulin (β2-MG) and kidney injury molecule-1(KIM-1) which indicated the nephrotoxicity induced by CCl4. Based on its strong antioxidant activity and its phenolic and terpenoid contents, CE significantly decreased oxidative damage and pro-inflammatory markers compared to CCl4 treated group.

CCl4

Cinnamon extract

Cinnamaldehyde

Renal damage

Biochemical parameters

Antioxidant

Carbon tetrachloride (CCl4) is a commonly industrial chemical that readily evaporates into the atmosphere (Fahmy, Diab, Abdel-Samie, Omara, & Hassan, 2018). The majority of its applications are currently prohibited due to its highly hazardous consequences. However, some industries continue to use it. Inhalation of CCl₄ fumes, dermal absorption, or intake on purpose as a suicide agent are the most common causes of human poisoning. Cellular damage caused by CCl₄ can be generated by the formation of covalent bonds between reactive intermediates and cellular components or by an increase in lipid peroxidation caused by free radical intermediates. It destroys lipids both within the cell and within the membrane (Johnston & Kroening, 1998).

Increased permeability of the membrane, which is a sign of akin cell damage, is caused by the breakdown products. CCl₄ induces severe damage in liver, kidneys and lungs. Acute kidney injury can be caused by CCl₄-induced nephrotoxicity, which can be caused by changes in intraglomerular hemodynamics, inflammation, rhabdomyolysis, microangiopathy, and tubular cell toxicity (Eric & Adolphus, 2020).

At the molecular level, tumour necrosis factor (TNF-α) and transforming growth factors (TGF-α and –ß) are all stimulated by CCl₄ which cause self-destruction or fibrosis in the cell (Dancey & Sausville, 2003).

Recently, plants represent a valuable source of raw materials for important drug discovery (Djordjevic, 2017). Herbal extracts have been shown to decrease CCl₄-induced oxidative stress by enhancing antioxidant enzyme activity and decreasing lipid peroxidation levels. (Rajesh & Latha, 2004).

Cinnamon is a valuable plant in herbal medicine. Cinnamaldehyde and cinnamic acid are the two most prominent chemical components of cinnamon (Wang, Wu, & Huo, 2007).

Based on its essential phytochemical ingredients such as phenolic and volatile organic compounds, cinnamon has been studied to investigate its different health advantages, including lowering triglycerides, low-density lipoprotein, and total cholesterol (Blevins et al., 2007), anti-inflammatory and antimicrobial activities, decreasing the probability of cardiovascular disease and colon cancer (Yeh et al., 2012), decreasing blood glucose level (Mollazadeh & Hosseinzadeh, 2016), antiangiogenesis (Hamidpour, Hamidpour, Hamidpour, & Shahlari, 2015), anti-yeast activity (Brr & Mahmoud, 2005), and improving blood circulation (Huang, Yuan, Kim, Quan, & Chung, 2011).

This study aimed to investigate the efficacy of cinnamon ethanolic extract (CE) to modulate the renal damage caused by CCl₄ through monitoring the oxidative stress and inflammatory markers as well as performing the histopathological analysis.

2.1. Plant materials and extraction process

The extraction was carried out at the Suez Canal University's chemistry department, faculty of science, in Ismailia, Egypt. The extraction process was carried out according to (Eidi, Mortazavi, Bazargan, & Zaringhalam, 2012). Briefly, cinnamon barks were bought from a public market, dried, milled, and extracted with 80% ethanol for 4 hours. The extraction process was performed in triplicate. After evaporation by rotary evaporator and drying using freeze dryer, the final dry powder was saved at -20°C in the dark until it was utilized in the study.

2.2. Total phenolic and flavonoids contents

Total flavonoid and phenolic contents of CE were determined according to Žilić, Serpen, Akıllıoğlu, Gökmen, and Vančetović (2012).

2.3. In vitro antioxidant assay

In vitro antioxidant activity of CE was analyzed using DPPH* method according to Hwang and Do Thi (2014).

2.4. Experimental animals

Twenty male Albino rats weighing approximately 180–200 g, were obtained from the animal lab, faculty of pharmacy, Suez Canal University. The animals were kept in stainless steel cages with a constant environmental temperature of 25 ± 3°C, humidity of 50–60%, and a 12 h:12 h light/dark cycle. Regular pellets and tap water were available to the animals at all times. The experiment was approved ethically by the Faculty of Veterinary Medicine, Suez Canal University ethical committee (approval no. 2021025).

2.5. Experimental design

CCl₄ was intraperitoneally administered as a positive renaltoxic agent twice a week for four weeks at a dose of 0.5 mL/kg according to Ogeturk et al. (2005). CE was crushed and suspended in 0.25 ml olive oil and used at a dose 0.1 g/kg b.w. daily for a period of four weeks (Eidi et al., 2012). Twenty rats were fasted overnight after a week of acclimation before being separated into four equal groups of five rats each; group I: serves as the normal control and fed on basal diet and received pure olive oil (0.25 ml/kg), group II: serves as the cinnamon extract control, Group III: serves as the CCl₄ control, Groups IV: received CCl₄ + CE at dose 0.1 g/kg b.w.

The animals were killed via cervical decapitation at the end of the experiment and kidney samples were divided into two pieces; one for histological investigation and the second was freezed for the determination of SOD, GSH, MDA, TNF-α, KIM-1 and ß2-MG.

2.6. Oxidative stress biomarkers

Malondialdehyde (MDA) was measured according to the manufacturer’s instructions (OxisResearch™, USA). MDA levels are a dependable sign of lipid peroxidation and oxidative stress in cells. The results were represented as µM MDA/milliliter kidney homogenate.

Glutathione reduced (GSH), glutathione is often regarded as the body's master antioxidant. GSH was measured according to the manufacturer’s instructions (OxiSelect™ Total Glutathione (GSSG/GSH) assay Kit, USA). The results were represented as µM GSH/milliliter kidney homogenate.

Superoxide dismutase (SOD), is a key antioxidative enzyme. SOD was measured according to the manufacturer’s instructions (OxiSelect™ Superoxide Dismutase Activity assay Kit, USA). The results were represented as U SOD/ µL kidney homogenate.

2.7. Tumor Necrosis Factor –alpha (TNF-α)

TNF- is thought to have a pro-inflammatory effect. It's the main mediator in immunological regulation. TNF-α was measured according to the manufacturer’s instructions (Immuno-Biological Laboratories, Inc., Rat TNF-α Assay Kit – IBL, USA). The results were represented as pg/mL kidney homogenate.

2.8. Kidney Injury Molecule-1 (Kim-1)

Kim-1 is become well-known as a useful tool for monitoring acute renal tubular damage in preclinical research. Kim-1 was measured in accordance with the manufacturer's specifications (OxiSelect™ Rat Kim-1 ELISA Kit, USA). The results were represented as pg/mL kidney homogenate.

2.9. β2-Microglobulin

β2-Microglobulin’s concentration varies in pathological circumstances such as glomerular edema, autoimmune disorders, malignant tumours, and hepatic edema. β2-Microglobulin was measured in accordance with the manufacturer's specifications (Kamiya Biomedical Company, USA). The results were represented as ng/mL kidney homogenate.

2.10. Histopathological assessment

Kidneys specimens were histopathologically analyzed according to Banchroft, Stevens, and Turner (1996). We used a semiquantitative scoring system to assess kidney lesions in accordance with Gibson-Corley, Olivier, and Meyerholz (2013). The renal lesions were assessed using renal tubular degeneration and hyaline cast formation.

2.11 Statistical analysis

The present results were analyzed using GraphPad Prism version 8 for windows. Results were expressed as Mean ± SD (n = 5). One-way ANOVA followed by Tukey’s test were used to examine the difference between groups. Significant was defined as a P value of less than 0.05

3.1. GC-MS analysis of CE

Phenylpropanoid and sesquiterpenes were found mainly in CE. These phytochemical constituents were identified by comparing with mass spectra stored in the database of the WILEY and NIST (Table 1). The major constituent was cinnamaldehyde.

Table 1

Chemical composition of CE, determined by gas chromatography–mass spectrometry analysis.
Peak	Retention Time	Name	Formula	Percentage (%)
1	19.173	Cinnamaldehyde, (E)-	C9H8O	95.92
2	22.218	Copaene	C15H24	2.25
3	26.749	.delta.-Cadinene	C15H24	1.25
4	26.069	.alpha.-Muurolene	C15H24	0.58

3.2. Total phenolic and flavonoid contents

Total phenolic content of CE calculated by Folin-Ciocalteu method was 183.91 mg GA/g. whereas, the total flavonoid content calculated by aluminum chloride (AlCl₃) colormetric assay was 139.37 mg CE/g.

3.3. Scavenging activity of DPPH radical:

CE showed activity of 252.22 mg TE/g which indicates its powerful ability to eliminate DPPH radical.

3.4. Antioxidants and lipid peroxidation

Table 2 illustrates the effect of CE treatment on antioxidants (GSH and SOD) and lipid peroxidation (as evaluated by malondialdehyde "MDA") in kidney tissue homogenate in CCl4-induced nephrotoxicity male rats. In the third positive CCl₄ treated group, antioxidants were significantly reduced, whilst lipid peroxidation was significantly elevated related to the first normal group. Treating the nephrotoxic fourth group with CE significantly raised antioxidant levels and lowered lipid peroxidation in the kidney tissue homogenate related to the CCl4 treated group.

3.5. Tumor necrosis factor alpha

Table 3 shows that TNF-α concentration in kidney tissue homogenate of the third positive CCl₄ treated group male rats was increased significantly related to the first normal control group. In the fourth group, treating the CCl4-administered rats with CE reduced TNF-α concentration relative to the positive CCl₄ group.

3.6. Kidney Injury Molecule-1

Table 3 shows that KIM-1 in kidney tissue homogenate of CCl₄ treated male rats was increased relative to the first normal control group. Treating the CCl₄ administered rats with CE in the fourth group decreased the KIM-1 levels compared to the positive CCl₄ treated group.

3.7. Beta 2-microglobulin

Table 3 shows that ß2-MG level in kidney tissue homogenate of CCl₄ treated male rats was increased relative to the first normal control group. Treating the CCl₄ administered rats with CE in the fourth group decreased the ß2-MG level compared to the positive CCl4 treated group.

Table 2

Effect of CE supplementation for 4 w on antioxidants and lipid peroxidation levels in kidney tissue homogenate of CCl4 treated male rat.
Parameter	Experimental groups
	Normal	Normal + extract	CCl4	CCl4 + extract
GSH	8.909 ± 0.07987^c,d	8.945 ± 0.1309^c,d	6.95 ± 0.1637^a,b,d	7.986 ± 0.1839^a,b,c
SOD	8.184 ± 0.06542 ^c,d	8.173 ± 0.05334 ^c,d	6.678 ± 0.1071 ^a,b,d	7.33 ± 0.1946 ^a,b,c
MDA	0.5023 ± 0.01006 ^c,d	0.5237 ± 0.003564 ^c,d	1.126 ± 0.022 ^a,b,d	0.9226 ± 0.01686 ^a,b,c
Each value represents the mean ± SD (n = 5)

Values in the same row having different superscript letters are significantly different at (P ≤ 0.05) as following:

a: significant difference compared with normal

b: significant different compared with normal + extract

c: significant different compared with CCl4

d: significant different compared with CCl4 + extract

Table 3

Effect of CE supplementation on TNF-α, KIM-1 and ß2-MG in tissue homogenate of CCl4 treated male rats.
Parameter	Experimental groups
	Normal	Normal + extract	CCl4	CCl4 + extract
TNF-α	8.357 ± 0.09284^c,d	8.287 ± 0.1169^c,d	14.45 ± 0.4344^a,b,d	11.08 ± 0.3318^a,b,c
KIM-1	2.483 ± 0.07211^c,d	2.438 ± 0.03713^c,d	3.581 ± 0.3497^a,b,d	3.003 ± 0.09051^a,b,c
ß2-MG	3.155 ± 0.006448^c,d	3.148 ± 0.004604^c,d	5.592 ± 0.08146^a,b,d	4.084 ± 0.0963^a,b,c
Each value represents the mean ± SD (n = 5)

Values in the same row having different superscript letters are significantly different at (P ≤ 0.05) as following:

a: significant difference compared with normal

b: significant different compared with normal + extract

c: significant different compared with CCl4

d: significant different compared with CCl4 + extract

3.8. Histopathological assessments

The kidney's cross section of control groups (group I & II) indicated typical glomeruli with intact basement membranes and normal capillary tufts, as well as a patent urine space. Tubules in the kidneys were likewise normal. Massive renal tubular nephrosis of both proximal and distal convolute tubules was found in Group III (CCl4 treated group). Degeneration, pyknotic nuclei, brush border loss, focal discrete necrosis of some tubular cells, hyaline cast forms inside tubular lumens, and blood vessel congestion were among the abnormalities. Except for minor epithelial degeneration and modest peritubular capillary congestion, the fourth treatment group (CCl4 + CE) demonstrated significant improvements.

CCl₄ damages cells in a variety of organs, primarily the liver, kidneys, and lungs (Teschke, 2018). The production of the CCl3 free radical and other metabolites causes CCl4 poisoning which harms cells through lipid peroxidation and other mechanisms. These free radicals may cause organ failure on several levels (Manno, Rezzadore, Grossi, & Sbrana, 1996). Our experiments were aimed to assess the efficacy of cinnamon extract in modulating the kidney damage caused by CCl4 by monitoring oxidative stress and inflammatory markers as well as performing histological analyses.

Our study involved four research stages in attempt to reach this research goal. The initial stage was studying the phytochemical constituents of CE and determining its antioxidant activity. DPPH, an unchanging nitrogen-centered violet coloured free radical, was used to assess the free radical scavenging potency. This assay relies on the reduction of an alcoholic DPPH solution to non-radical yellow-colored diphyenylpicrylhydrazine. As a result, the radical scavenging effectiveness of plant extracts is determined by measuring a drop in DPPH absorbance caused by colour variation. The strong antioxidant properties of CE was attributed mainly to the presense of terpenoid compounds, as cinnamaldehyde. Further, the polyphenolic compounds present in CE may also contribute to this antioxidant activity. The phenolic group can accept an electron and forming relatively stable phenoxyl radicals which disrupt the chain oxidation reaction (Pandey & Rizvi, 2009).

The second stage of our work was investigating the oxidative stress alterations caused by individual and combined treatment with CCl₄ and CE. The oxidative stress biomarkers were examined. When the pro-oxidant/antioxidant equilibrium is altered toward the pro-oxidants, oxidative stress occurs. The presence of polyunsaturated fatty acids in cellular membranes causes oxidative damage, and lipid perioxidation is a useful marker for studying this. MDA is a lipid perioxidation end product that binds to the protein's sulfhydryl groups and has the capacity to crosslink the protein, decreasing or eliminating it (Ayala, Muñoz, & Argüelles, 2014). When compared to the control group, CCl4 caused oxidative stress, as demonstrated by a significant rise in kidney homogenate MDA and a significant drop in kidney homogenate GSH and SOD levels.

Increased MDA levels are linked to a decrease of membrane fluidity and the antioxidant defence systems' inability to scavenge free radicals. All of these variables contribute to tissue damage (Al-Olayan, El-Khadragy, Metwally, & Moneim, 2014). Antioxidant enzymes like SOD and GSH help to protect the body from reactive oxygen species (ROS) and environmental damage. Glutathione acts as a primary line of defence against ROS. Furthermore, GSH-dependent enzymes provide an important line of defence by detoxifying the toxic byproducts produced by ROS. Increased GSH use against peroxides could explain the lower GSH levels in the kidney. Many investigations have shown that GSH plays a critical role in the elimination of CCl4's toxic metabolites, and that organ harm begins when GSH levels are severely reduced (Boshy et al., 2017). These finding agreed with Bellassoued et al. (2019) who demonstrated that giving rats cinnamon essential oil had a great potential for quenching free radicals and alleviating CCl4-induced hepatorenal damage.

As highlighted in our study, CE significantly reduced MDA levels while considerably increasing GSH and SOD levels in CCl4-intoxicated groups, reversing oxidative stress. These findings indicated that CE has a strong antioxidant properties that reduced oxidative stress and helped to restore damaged cells. These findings illustrated that CE's antiradical scavenging is one of the most important mechanisms for preventing cellular damage.

Monitoring the measures of inflammation and kidney damage generated by individual and combined therapy with CCl4 and CE was the third stage of our research. TNF-α is an inflammatory cytokine that is released during acute inflammation and is involved in a variety of signalling pathways within cells that result in necrosis or apoptosis. This protein is also valuable for infection and cancer resistance (Idriss & Naismith, 2000). TNF- levels in CCl4-treated rats' renal tissues homogenate are much higher than in normal control rats. These findings supported Mazani et al. (2020) whose findings revealed that CCL4 injection causes the liver and kidney tissues to produce pro-inflammatory cytokines including IL-6 and TNF-α.

Inhibiting inflammation is a crucial step in reducing CCl4's damage. Our results showed that CE can alleviate against CCl₄-induced nephrotoxicity as evidenced by significant decrease in TNF-α concentration in rats’ kidney homogenate. Our findings are agreed with earlier studies, where the expression level of TNF-α was significantly reduced by polyphenolic compounds administration due to their anti-inflammatory activity (Yahfoufi, Alsadi, Jambi, & Matar, 2018).

Kidney Injury Molecule (KIM-1) aids in the phagocytic clearance of apoptotic and necrotic cells during renal injury (Han, Bailly, Abichandani, Thadhani, & Bonventre, 2002). Based on our knowledge, no research has been published on the effect of CE treatment on KIM-1 expression. Compared to normal rats, KIM-1 level in kidney tissue homogenates of CCl4 treated rats are considerably higher. These finding are in the same line with Potić et al. (2019) who reported that CCl4 promotes parenchymatous degeneration in S1/S2 segments of proximal tubules, implying that KIM-1 expression will rise in those regions. Tubulocytes that express KIM-1 are able to phagocyte luminal apoptotic debris, allowing renal tissue to recover and the inflammatory response to be reduced (Zuk & Bonventre, 2016). Autophagy is being considered as a potential pharmacological target for treating some kidney problems as it can allow severely damaged cells to remain and cause harm (Baisantry et al., 2016).

CE significantly decreased KIM-1 level in renal tissue homogenates of CCl₄ treated rats compared to rats treated with CCl₄ only. The ameliorative effect of CE could be attributed to its flavonoid content. (Ren et al., 2020) found that flavonoid compound inhibited induced mRNA level of KIM-1.

The change in the concentration of the conventional biochemical marker β2-MG was used to identify the indication of kidney injury (Popović et al., 2019). Almost all nucleated cells have β2-MG on their membrane surface. Increased levels of β2-MG have been linked to a variety of illnesses, including inflammation, hepatic or renal disorders, viral infections, and various cancers. (Li, Dong, & Wang, 2016).

In comparison to normal rats, CCl4 treatment resulted in a considerable rise in β2-MG levels in renal tissue homogenates. In comparison to CCl4-treated rats, CE dramatically reduced β2-MG levels in kidney tissue homogenates. The ameliorative effect of CE is attributed mainly to its high content of cinnamaldehyde which results in decreased expression of β2-MG mRNA (El Ali, Deloménie, Botton, Pallardy, & Kerdine-Römer, 2017).

The fourth stage of our research looked at the renal histological structure after treatment with CCl4 and CE separately and in combination. CE treatment reduced CCl4 damage in the kidneys, according to histological evaluations. CE's antioxidant properties helped to reduce oxidative kidney damage.

The injection of CCl4 to kidney tissues caused oxidative stress, as shown by increased MDA and decreased GSH and SOD levels in kidney homogenate. Also, CCl4 caused renal damage which evidenced by increased TNF-α concentration, KIM-1 and β2-MG levels in kidney homogenate. Interestingly, the concomitant administration of CE was remarkably alleviated renal damage induced by CCl₄. CE dramatically boosted the activity of the antioxidant defense enzyme SOD and GSH, and lowering the CCl4-elevated MDA level. CE significantly repaired the renal histo-architecture lesions generated in CCl4-treated rats to their normal histological structures. The high phenolic, flavonoid, and terpenoid contents of CE may explain its protective activity against CCl4-induced kidney injury. These findings might provide a natural approach to the treatment of CCl4 poisoning.

Declarations of interest

The authors have no relevant financial or non-financial interests to disclose.

Author Contributions

All authors have contributed to the manuscript in significant way, have reviewed and agreed upon the manuscript content.

Authors’ contribution: Ohoud Marie: Conceptualization, laboratory work, Writing - Review & Editing, Statistical Analysis and writing final draft. Amany Tawfik: Data curation and Writing the first draft. Amina Dessouki: Methodology, laboratory work and Supervision Mohamed Omar: Conceptualization, data curation and Writing the first draft.

Al-Olayan EM, El-Khadragy MF, Metwally DM, Moneim AEA (2014) Protective effects of pomegranate (Punica granatum) juice on testes against carbon tetrachloride intoxication in rats. BMC Complement Altern Med 14(1):1–9
Ayala A, Muñoz MF, Argüelles S (2014) Lipid peroxidation: production, metabolism, and signaling mechanisms of malondialdehyde and 4-hydroxy-2-nonenal. Oxidative Medicine and Cellular Longevity, 2014
Baisantry A, Bhayana S, Rong S, Ermeling E, Wrede C, Hegermann J, Melk A (2016) Autophagy induces prosenescent changes in proximal tubular S3 segments. J Am Soc Nephrol 27(6):1609–1616
Banchroft J, Stevens A, Turner D (1996) Theory and practice of histological techniques: Churchil Livingstone, New York, London, San Francisco, Tokyo
Bellassoued K, Ghrab F, Hamed H, Kallel R, Pelt Jv, Lahyani A, Feki AE (2019) Protective effect of essential oil of Cinnamomum verum bark on hepatic and renal toxicity induced by carbon tetrachloride in rats. Appl Physiol Nutr Metab 44(6):606–618. 10.1139/apnm-2018-0246%M 30994004
Blevins SM, Leyva MJ, Brown J, Wright J, Scofield RH, Aston CE (2007) Effect of cinnamon on glucose and lipid levels in Non–insulin-dependent type 2 diabetes. Diabetes Care 30(9):2236–2237
Boshy M, Abdelhamidb F, Richab E, Ashshia A, Gaitha M, Qustya N (2017) Attenuation of CCl4 induced oxidative stress, immunosuppressive, hepatorenal damage by fucoidan in rats. J Clin Toxicol 7(3):1–7
Brr A-AH, Mahmoud YA-G (2005) Anti-yeast effects of some plant extracts on yeasts contaminating processed poultry products in Egypt. Czech J Food Sci Vol 23(1):12–19
Dancey J, Sausville EA (2003) Issues and progress with protein kinase inhibitors for cancer treatment. Nat Rev Drug Discovery 2(4):296–313
Djordjevic S (2017) From Medicinal Plant Raw Material to Herbal Remedies
Eidi A, Mortazavi P, Bazargan M, Zaringhalam J (2012) Hepatoprotective activity of cinnamon ethanolic extract against CCI4-induced liver injury in rats. EXCLI J 11:495–507
El Ali Z, Deloménie C, Botton J, Pallardy M, Kerdine-Römer S (2017) Dendritic cells' death induced by contact sensitizers is controlled by Nrf2 and depends on glutathione levels. Toxicol Appl Pharmacol 322:41–50. doi: 10.1016/j.taap.2017.02.014
Eric E, Adolphus E (2020) Ameliorative Effects of Turmeric Extract against CCL4 Induced Liver and Kidney Injury in Adult Wistar Rat.Asian Journal of Immunology,36–42
Fahmy MA, Diab KA, Abdel-Samie NS, Omara EA, Hassan ZM (2018) Carbon tetrachloride induced hepato/renal toxicity in experimental mice: antioxidant potential of Egyptian Salvia officinalis L essential oil. Environ Sci Pollut Res 25(28):27858–27876
Gibson-Corley KN, Olivier AK, Meyerholz DK (2013) Principles for valid histopathologic scoring in research. Vet Pathol 50(6):1007–1015
Hamidpour R, Hamidpour M, Hamidpour S, Shahlari M (2015) Cinnamon from the selection of traditional applications to its novel effects on the inhibition of angiogenesis in cancer cells and prevention of Alzheimer's disease, and a series of functions such as antioxidant, anticholesterol, antidiabetes, antibacterial, antifungal, nematicidal, acaracidal, and repellent activities. J traditional Complement Med 5(2):66–70
Han WK, Bailly V, Abichandani R, Thadhani R, Bonventre JV (2002) Kidney Injury Molecule-1 (KIM-1): a novel biomarker for human renal proximal tubule injury. Kidney Int 62(1):237–244. doi: 10.1046/j.1523-1755.2002.00433.x
Huang B, Yuan HD, Kim DY, Quan HY, Chung SH (2011) Cinnamaldehyde prevents adipocyte differentiation and adipogenesis via regulation of peroxisome proliferator-activated receptor-γ (PPARγ) and AMP-activated protein kinase (AMPK) pathways. J Agric Food Chem 59(8):3666–3673
Hwang E-S, Do Thi N (2014) Effects of extraction and processing methods on antioxidant compound contents and radical scavenging activities of laver (Porphyra tenera). Prev Nutr Food Sci 19(1):40
Idriss HT, Naismith JH (2000) TNFα and the TNF receptor superfamily: Structure-function relationship (s). Microsc Res Tech 50(3):184–195
Johnston DE, Kroening C (1998) Mechanism of early carbon tetrachloride toxicity in cultured rat hepatocytes. Pharmacol Toxicol 83(6):231–239
Li L, Dong M, Wang X-G (2016) The Implication and Significance of Beta 2 Microglobulin: A Conservative Multifunctional Regulator. Chin Med J 129(4):448–455. doi: 10.4103/0366-6999.176084
Manno M, Rezzadore M, Grossi M, Sbrana C (1996) Potentiation of occupational carbon tetrachloride toxicity by ethanol abuse. Hum Exp Toxicol 15(4):294–300. doi: 10.1177/096032719601500404
Mazani M, Rezagholizadeh L, Shamsi S, Mahdavifard S, Ojarudi M, Salimnejad R, Salimi A (2020) Protection of CCl4-induced hepatic and renal damage by linalool.Drug and Chemical Toxicology,1–9
Mollazadeh H, Hosseinzadeh H (2016) Cinnamon effects on metabolic syndrome: a review based on its mechanisms. Iran J basic Med Sci 19(12):1258
Ogeturk M, Kus I, Colakoglu N, Zararsiz I, Ilhan N, Sarsilmaz M (2005) Caffeic acid phenethyl ester protects kidneys against carbon tetrachloride toxicity in rats. J Ethnopharmacol 97(2):273–280. doi: https://doi.org/10.1016/j.jep.2004.11.019
Pandey KB, Rizvi SI (2009) Plant polyphenols as dietary antioxidants in human health and disease. Oxidative Med Cell Longev 2(5):270–278
Popović D, Kocić G, Katić V, Jović Z, Zarubica A, Veličković LJ, Rakić V (2019) Protective effects of anthocyanins from bilberry extract in rats exposed to nephrotoxic effects of carbon tetrachloride. Chem Biol Interact 304:61–72
Potić M, Ignjatović I, Ničković VP, Živković JB, Krdžić JD, Mitić JS, Sokolović D (2019) Two different melatonin treatment regimens prevent an increase in kidney injury marker-1 induced by carbon tetrachloride in rat kidneys. Can J Physiol Pharmacol 97(5):422–428. 10.1139/cjpp-2018-0641%M 30730758
Rajesh M, Latha M (2004) Protective activity of Glycyrrhiza glabra Linn. on carbon tetrachloride-induced peroxidative damage. Indian J Pharmacol 36(5):284
Ren Q, Guo F, Tao S, Huang R, Ma L, Fu P (2020) Flavonoid fisetin alleviates kidney inflammation and apoptosis via inhibiting Src-mediated NF-κB p65 and MAPK signaling pathways in septic AKI mice. Biomed Pharmacother 122:109772
Teschke R (2018) Liver Injury by Carbon Tetrachloride Intoxication in 16 Patients Treated with Forced Ventilation to Accelerate Toxin Removal via the Lungs: A Clinical Report. Toxics 6(2). doi: 10.3390/toxics6020025
Wang M, Wu M, Huo H (2007) Life-cycle energy and greenhouse gas emission impacts of different corn ethanol plant types. Environ Res Lett 2(2):024001
Yahfoufi N, Alsadi N, Jambi M, Matar C (2018) The Immunomodulatory and Anti-Inflammatory Role of Polyphenols. Nutrients 10(11):1618. doi: 10.3390/nu10111618
Yeh H-C, Brown TT, Maruthur N, Ranasinghe P, Berger Z, Suh YD, Bass EB (2012) Comparative effectiveness and safety of methods of insulin delivery and glucose monitoring for diabetes mellitus: a systematic review and meta-analysis. Ann Intern Med 157(5):336–347
Žilić S, Serpen A, Akıllıoğlu Gl, Gökmen V, Vančetović J (2012) Phenolic compounds, carotenoids, anthocyanins, and antioxidant capacity of colored maize (Zea mays L.) kernels. J Agric Food Chem 60(5):1224–1231
Zuk A, Bonventre JV (2016) Acute kidney injury. Annu Rev Med 67:293–307

Download PDF

Version 1

posted

You are reading this latest preprint version

Renal protective effect of Cinnamon ethanolic extract against induced renal damage by carbon tetrachloride administration in rats

Status:

Version 1

Abstract

Figures

1. Introduction

2. Materials And Methods

2.1. Plant materials and extraction process

2.2. Total phenolic and flavonoids contents

2.3. In vitro antioxidant assay

2.4. Experimental animals

2.5. Experimental design

2.6. Oxidative stress biomarkers

2.7. Tumor Necrosis Factor –alpha (TNF-α)

2.8. Kidney Injury Molecule-1 (Kim-1)

2.9. β2-Microglobulin

2.10. Histopathological assessment

2.11 Statistical analysis

3. Results

3.1. GC-MS analysis of CE

3.2. Total phenolic and flavonoid contents

3.3. Scavenging activity of DPPH radical:

3.4. Antioxidants and lipid peroxidation

3.5. Tumor necrosis factor alpha

3.6. Kidney Injury Molecule-1

3.7. Beta 2-microglobulin

3.8. Histopathological assessments

4. Discussion

Conclusion

Statements & Declarations

References

Status:

Version 1