In this study, the effects of vitamin E on the adrenal gland were investigated in the immobilization stress model. Mice were subjected to immobilization stress six hours a day for one week. Our results revealed that stress-induced structural changes such as cortical atrophy, medullary hypertrophy, dilated capillaries, fibrosis, and hemorrhage were observed in the adrenal gland, confirming the findings of previous studies. [4, 20, 21] Moreover, we have demonstrated that vitamin E has a protective effect on these stress-induced changes.
Stress is a process that plays an active role in the pathogenesis of various diseases in rodents by deteriorating the physical, biochemical, and psychological parameters.  A study showed that stress has the potential to increase symptoms of anxiety and depression.  In this study, immobilization stress also caused severe anxiety-like behavior and depression as compared with unstressed animals. Experimental studies demonstrated that vitamin E has antidepressant-like effects. [24, 25] The depression level of the mice in the stress group increased significantly in the forced swimming test, while the depression level of the vitamin E group was decreased (Figs. 1,2 and 3).
Exposure to stress may elevate the production of free radicals and impair the antioxidant defense system, leading to oxidative damage and imbalance between oxidant and antioxidant factors. [26–28] We measured MDA (a biomarker of lipid peroxidation) levels, which was the highest in the stress group. MDA levels in the vitamin E treated groups were significantly lower than that of the stress group (Fig. 4). These results confirmed that vitamin E has antioxidant effects that can protect the adrenal gland tissue from stress-induced oxidative stress.
Exposure to immobilization stress also causes histopathological changes in the stomach, intestine, testis, and adrenal gland in male rats. [29–31] Morphometric measurements revealed that capsule and cortex thickness significantly decreased in the stress group (Fig. 3). Studies have shown that the zona glomerulosa is the major zone of mitosis and that the zona reticularis is the region with most cell deaths. [32–34] The histochemical observations in the present work showed that the control and vitamin E groups indicated similar histological appearances (Fig. 7a, c). Cortical atrophy was observed in the stress and stress + vitamin E groups. This was because of the balance between mitosis and cell death. In our case the balance was in favor of cell death. However, atrophy in the stress + vitamin E group was lower than in the stress group, suggesting vitamin E induces cortical cells to drive mitosis. Vascular dilatation, congestion, and hemorrhage were also seen in this group. Generally, the stress + vitamin E group showed histology similar to the control group (Fig. 7b,d).
El-Refaiy  and Rai et al [36, 37] showed that exposure to stress increased fibroblasts and collagen fiber synthesis, leading to the thickening of the testis basement membrane. Furthermore, increased fibrosis in the colon mucosa of rats exposed to stress due to collagen synthesis has also been documented.  El-Desouki et al.  stated that immobilized stress ultrastructurally caused elevated levels of collagen fibers in the rat adrenal cortex. In the AZAN-stained sections, the control group and the vitamin E group showed no fibrosis (Fig. 8a, c). Interstitial fibrosis through the adrenal cortex was seen in the stress group, but dense fibrosis was observed in the corticomedullary region. Excessive vascular dilatation, congestion, and hemorrhage were also observed in the stress group. In the stress + vitamin E group, those symptoms were mostly recovered, but signs of fibrosis were still evident (Fig. 8b, d).
In conclusion, immobilization stress may be responsible for the psychopharmacological, morphometric, and histochemical changes in the immobilization stress-induced mouse adrenal gland, and vitamin E may be protective against these alterations.