Angiotensin II Type 1 receptor blockade attenuates the neuropathological changes in the spinal cords of diabetic rats with modulation of nuclear factor erythroid 2-related factor 2/ heme oxygenase 1 system.

Peripheral and central neuropathies frequently complicate worldwide diabetes. Compared to peripheral neuropathy, central neuropathy didn`t gain a major research interest. Angiotensin II is reported to be involved in diabetic neuropathic pain but its role in the central pathological changes in the spinal cord is not clear. Here, we study the role of Losartan; an Angiotensin II receptor 1 (AT1) antagonist in suppression of the diabetes-induced changes in the spinal cord. Three groups of rats were applied; a negative control group, a streptozotocin (STZ) diabetic group, and a group receiving STZ and Losartan. After two months, the pathological alteration in the spinal cord was investigated, and an immunohistochemical study was performed for neuronal, astrocytic, and microglial markers; nuclear protein (NeuN), Glial fibrillary acidic protein (GFAP), and Ionized calcium-binding adaptor molecule 1 (Iba1), respectively, and for an apoptosis marker; caspase-3, and the inflammatory marker; nuclear factor kappa B (NF-kB) signaling, heme oxygenase-1 (HO-1) and nuclear factor erythroid 2-related factor 2 (Nrf2); physiological antioxidant system. The results showed that Losartan caused recovery of spinal cord changes, by inhibiting the microglial and astrocytic activation, suppressing neuronal apoptosis and NF-kB expression with activation of Nrf2/HO-1 (P<0.0005). It is suggested, herein, that Losartan can suppress diabetes-induced glial activation, inflammation, neuronal apoptosis, and oxidative stress in the spinal cord; the mechanisms that may underlie the role of AT1 antagonism in suppressing diabetic neuropathic pain.

Effect of Sofosbuvir on rats' ovaries and the possible protective role of vitamin E: biochemical and immunohistochemical study.

Hepatitis C virus (HCV) infection is a major health problem worldwide and its eradication is mandatory. Direct acting HCV polymerase inhibitors, such as Sofosbuvir (SOF), is an effective regimen. However, it has some side effects like mutagenesis, carcinogenesis, and the impairment of testicular function. It is important to evaluate the safety of SOF on the ovary, as there are no studies yet. Increasing the production of Reactive Oxygen Species (ROS), causes oxidative stress, which affects ovulation process, female reproduction, and fertility. Accumulation of SOF in the cells was demonstrated to promote ROS generation. Vitamin E (Vit E) is an antioxidant agent that has an essential role in the female reproductive system, its deficiency can cause infertility. We explored the effect of SOF treatment alone and co-treated with Vit E on ovarian ROS level and ovarian morphology experimentally using biochemical and immunohistochemical studies. Significant changes in oxidative stress markers; nitric oxide and malondialdehyde lipid peroxidation, antioxidant enzymes; catalase, super oxide dismutase, and reduced glutathione, proliferating markers; proliferation cell nuclear antigen and Ki-67 antigen and caspase 3 apoptotic marker were demonstrated. It was shown that where SOF induced oxidative stress, it also aggravated ovarian dysfunction. The essential role of Vit E as an antioxidant agent in protecting the ovarian tissue from the effect of oxidative stress markers and preserving its function was also displayed. This could be guidance to add Vit E supplements to SOF regimens to limit its injurious effect on ovarian function.

The neuroprotective effect of simvastatin on the cerebellum of experimentally-induced diabetic rats through klotho upregulation: An immunohistochemical study.

BACKGROUND: Diabetes mellitus is a multifactorial metabolic disorder that is complicated by multi-organ dysfunction including CNS. Klotho is an anti-aging protein expressed in Purkinje cells of the cerebellum. Klotho protects against the development of several neurodegenerative diseases. Simvastatin is a lipophilic statin that can enhance klotho expression. AIM OF THE STUDY: This study was designed to investigate cerebellar structural changes in diabetes, klotho expression in the cerebellum of diabetic rats and the neuroprotective effect of simvastatin. MATERIALS & METHODS: 24 adult albino rats were divided into 4 groups; control, simvastatin, diabetic (induced by single intraperitoneal injection of STZ 45 mg/kg) and diabetic treated by simvastatin (10 mg/kg once daily) after confirmation of diabetes. Rotarod test was performed for evaluation of motor coordination. Blood glucose and insulin levels were estimated for confirmation of diabetes. Reduced glutathione (GSH) and malonaldehyde (MDA) in cerebellar tissues were evaluated. The cerebellar samples were prepared for histological and immunohistochemical staining. RESULTS: The latency time on the rotarod was reduced in diabetic rats. Cerebellar structure was disturbed in diabetic group. Oxidative stress was evidenced by increased MDA and reduced GSH. Klotho expression was downregulated and caspase-3 was increased in diabetes. Simvastatin increased the latency time. Simvastatin diminished the changes in oxidative stress markers and succeeded to ameliorate the diabetic induced cerebellar changes. Simvastatin enhanced Klotho and diminished Caspase-3 expression. CONCLUSION: Simvastatin can ameliorate diabetic induced cerebellar changes through minimizing oxidative stress, enhancement of Klotho expression and reduction of apoptosis.