Acrylamide (ACRL) was demonstrated to induce hepatotoxicity and programmed cell death (PCD). Rapamycin (RAPA)‐induced autophagy had been reported to limit the progression of hepatocellular injury in experimental models. This research was designed to study two death pathways involved in ACRL‐induced hepatotoxicity and the modulating effect of RAPA on the resulting hepatic injury. Thirty‐six adult male rats were divided into three groups: control group, ACRL‐treated group (20 mg kg/day), and the last group co‐treated with ACRL plus RAPA (0.5 mg kg/day). Drugs were administered for 21 days via oral gavage. Blood samples were collected to assess alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Livers were dissected; parts were used for detection of superoxide dismutase (SOD) and malondialdehyde (MDA) tissue levels. Other parts were processed for hematoxylin and eosin, Masson's trichrome staining, immunostaining for microtubule‐associated proteins 1A/1B light chain 3B (LC3), ubiquitin‐binding protein (p62), caspase‐3, and receptor‐interacting protein kinase 1 (RIPK1). ACRL induced a significant elevation in ALT, AST, MDA levels, and reduction in the SOD level. ACRL also induced hepatocellular injury, fibrosis, and defective autophagy indicated by elevation of LC3 and p62 and increased p62/LC3 ratio. Moreover, it increased the apoptotic (caspase‐3) and necroptotic (RIPK1) markers expression. RAPA significantly reduced liver enzymes, oxidative stress, fibrosis, and improved liver histology. Moreover, RAPA decreased p62/LC3 ratio indicated enhanced autophagy, and significantly reduced caspase‐3 and RIPK1 expression. In conclusion, RAPA maintained autophagic activity which may save the hepatocytes from PCD and enhance cell viability.

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Lithium containing drugs are the drugs of choice for the treatment of bipolar disorder, preventing recurrence and suicide attempts. Recently, lithium may be used to encourage growth of gray matter in the cerebral cortex and to prevent progression of Alzheimer's disease, senile dementia and Parkinson's disease. The present study was designed to study the toxic effect of lithium on albino rat kidneys and the possible protective effect of vitamin E. Thirty-two adult male albino rats were used. They were divided into 4 groups of eight rats each (control group, lithium carbonate treated group, lithium carbonate plus vitamin E treated group and vitamin E treated group). In the experimental groups, lithium treated group received daily intraperitoneal injection of 50 mg/kg of lithium carbonate dissolved in 0.9% NaCL divided in 2 doses for 4 weeks. Lithium and vitamin E treated group received lithium carbonate (50 mg/kg) and intraperitoneal injection of vitamin E (50 mg/kg) dissolved in olive oil once daily for 4 weeks. Blood samples were collected from all groups at the end of the experiment for serum creatinine level measurement. Kidneys were dissected rapidly, fixed in 10% formalin, processed and stained with haematoxylin and eosin, PAS, Masson trichrome stains and with immunohistochemical stains for bax and αsma. Kidneys of lithium carbonate treated rats showed degenerated renal tubules, distorted glomeruli with loss of apical brush border of the proximal convoluted tubules and high expression of bax and αsma stains. A significant increase in the serum creatinine levels and a significant decrease in the diameter of renal glomeruli were observed 4 weeks after lithium administration. Addition of vitamin E to lithium resulted in less renal degenerative changes and less expression of bax and αsma stains with a highly significant decrease in serum creatinine levels compared with lithium carbonate treated group. It was concluded that the harmful effect of lithium on the kidneys should be closely monitored in patients taking lithium containing drugs and it could be attenuated by additional use of vitamin E.Personal non-commercial use only. EJA