Bisphenol A (BPA) is a key monomer in the production of plastics. It has been shown to be hepatotoxic. Inflammation and oxidative stress are closely linked with liver fibrosis, the major contributing factor to hepatic failure. Therefore, the aim of this study was to evaluate the impact of chronic exposure to BPA on the development of hepatic fibrosis in male rats and to determine the cross-talk between the hepatic cytokine network, oxidative stress and apoptosis. For this purpose, 30 male Wistar albino rats were divided into three equal groups as follows: the first group was given no treatment (normal control group); the second group was given corn oil once daily by oral gavage for 8 weeks (vehicle control group); and the third group received BPA (50 mg/kg body weight/day, p.o.) for 8 weeks. BPA administration induced liver fibrosis as reflected in an increase in serum hepatic enzymes activities, hepatic hydroxyproline content and histopathological changes particularly increased collagen fibre deposition around the portal tract. In addition, there was inflammation (as reflected in increase in interleukin-1beta 'IL-1β', decrease in interleukin-10 'IL-10' serum levels and increase in IL-1β/IL-10 ratio), oxidative stress (as reflected in increase in malondialdehyde (MDA) level, reduction in reduced glutathione (GSH) content and inhibition of catalase (CAT) activity) and apoptosis [as reflected in an increase in caspase-3 level and a decrease in numbers of B-cell lymphoma 2 (BCL2)-immunopositive hepatocytes]. Interestingly, BPA had an upregulating effect on an extracellular matrix turnover gene [as reflected in matrix metalloproteinase-9 (MMP-9)] and a downregulating effect on its inhibitor gene [as reflected in tissue inhibitor of matrix metalloproteinase-2 (TIMP-2)] expression. Thus, the mechanism by which BPA induced liver fibrosis seems to be related to stimulation of the inflammatory response, along with oxidative stress, the apoptotic pathway and activation of extracellular matrix turnover.
BackgroundDiabetes and cerebral ischemic-reperfusion are among the most common causes of neurological complications in Egypt. The prevalence of diabetes in Egypt is high and it can be considered as a major clinical and public health problem.MethodsBlood glucose, lipid profile, oxidative stress makers (cerebral MDA & GSH), cerebral interleukin-4 (IL-4) level and cerebral cyclooxygenase-2 (COX-2) gene expression were measured in male albino rats weighing 200 ± 20 g. The rats were divided into five groups, normal control group, diabetic group (diabetes was induced by single dose of streptozotocin [STZ]), diabetic cerebral ischemic-reperfused group, two treated groups (diabetic and diabetic ischemic-reperfused), both groups treated with resveratrol. Histological study was done using H&E, AgNOR and cresyl violet stains. Immunohistochemistry for Bax and COX-2 was done with morphometric study.ResultsDiabetic and diabetic cerebral ischemic- reperfused rats showed significant increase in serum glucose level, serum TAG, serum LDL-C, atherogenic index, cerebral MDA and upregulation of COX-2 gene expression. These groups showed significant decrease in serum HDL, cerebral IL-4 and depletion of cerebral GSH when compared to normal control rats. Treating these groups with resveratrol resulted in significant decrease in serum glucose level, serum TAG, TC, serum LDL-C, atherogenic index, cerebral MDA and downregulation of COX-2 gene expression. The results of COX-2 gene expression were confirmed by COX-2 immunohistochemistry. Also, significant increase in serum HDL, cerebral IL-4 and cerebral GSH contents could be observed in these treated groups as compared to normal control group. Cerebral apoptotic index and optical density of Bax reaction revealed significant increase in diabetic and diabetic cerebral ischemic-reperfused rats while treatment of these groups with resveratrol resulted in significant decrease in cerebral apoptotic index and optical density of Bax reaction. These apoptotic results were confirmed with AgNOR and cresyl violet stains.ConclusionThe results of this research suggest that upregulation of cerebral COX-2 gene along with the decrease in cerebral IL-4 and enhanced cerebral apoptosis is critically involved in cerebral damage associated with diabetes and cerebral ischemic-reperfusion. Resveratrol can ameliorate these effects and has promising neuroprotective effect in diabetic-induced cerebral complications.
Chronic kidney disease may lead to subsequent tissue fibrosis. However, many factors can combat injurious stimuli in these tissues aiming to repair, heal, and alleviate any disturbance. Chemokines release, migration of inflammatory cells to the affected site, and activation of fibroblasts for the production of extracellular matrix are commonly observed in this disease. In the last years, many studies have focused on spironolactone (SPL), a mineralocorticoid receptor antagonist, and its pharmacological effects. In the present study, SPL was selected as an anti-inflammatory agent to combat nephrotoxicity and renal fibrosis induced by cisplatin. Mesenchymal stem cells (MSCs) were also selected in addition as a referring agent. Renal fibrosis induced by cisplatin intake significantly increased creatinine, urea, nuclear factor kappa B, insulin-like growth factor-1, fibroblast growth factor-23, and kidney malondialdehyde (MDA) content. Hepatocyte growth factor and renal content of reduced glutathione demonstrated a significant decrease. Histopathological examination of kidney tissues demonstrated marked cellular changes which are correlated with the biochemical results. Oral SPL intake (20 mg/kg/body weight) daily for 4 weeks and MSCs administration (3 × 10 cell/rat) intravenous to the experimental rats resulted in a significant improvement of both the biomarkers studied and the histopathological profile of the renal tissue. Individual administration of spironolactone and MSCs exhibited a marked anti-inflammatory potential and alleviated to a great extent the nephrotoxicity and renal fibrotic pattern induced by cisplatin.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.