Hexavalent chromium (CrVI) is a heavy metal widely used in more than 50 industries. Nephrotoxicity is a major adverse effect of chromium poisoning. The present study investigated the potential renoprotective effect of lactoferrin (Lf) against potassium dichromate (PDC)-induced acute kidney injury (AKI) in rats. Beside, because previous studies suggest that interlukin-18 (IL-18) and insulin-like growth factor-1 (IGF-1) play important roles in promoting kidney damage, the present work aimed to evaluate the involvement of these two cytokines in PDC model of AKI and in the potential renoprotective effect of lactoferrin. Adult male albino Wistar rats were pretreated with Lf (200mg/kg/day, p.o.) or (300mg/kg/day, p.o.); the doses that are usually used in the experiment studies, for 14 days followed by a single dose of PDC (15mg/kg, s.c.). PDC caused significant increase in serum urea, creatinine, and total protein levels. This was accompanied with decreased renal glutathione content, and increased renal malondialdehyde, IL-18, IL-4, nuclear factor kappa B (NFκB), IGF-1, and the phosphorylated form of forkhead box protein O1 (FoxO1) levels. Moreover, normal expression IFN-γ mRNA and enhanced expression of TNF-α mRNA was demonstrated in renal tissues. Histopathological investigations provoked deleterious changes in the renal tissues. Tubular epithelial hyperplasia and apoptosis were demonstrated immunohistochemically by positive proliferating cell nuclear antigen (PCNA), Bax, and Caspase-3 expression, respectively. Pretreatment of rats with Lf in both doses significantly corrected all previously mentioned PDC-induced changes with no significant difference between both doses. In conclusion, the findings of the present study demonstrated the involvement of oxidative stress, inflammatory reactions, tubular hyperplasia and apoptosis in PDC-induced AKI. It suggested a role of IL-18 through stimulation of IL-4-induced inflammatory pathway, and IGF-1 through triggering FoxO1-induced cell proliferation. Moreover, the study revealed that Lf protected the kidney against Cr-induced AKI in rats and significantly showed antioxidant, anti-inflammatory, and anti-proliferative properties with down-regulation of IL-18 and IGF-1.

Background: Diethylnitrosamine (DENA), a well-known dietary carcinogen, related to cancer initiation of variousorgans. The present study investigated the deleterious mechanisms involved in the early destructive changes of DENAin different organs namely, liver, stomach and colon and the potential protective effect of GE against these mechanisms.Methods: Adult male albino rats were assigned into four groups. A normal control group received the vehicle, anothergroup was injected with a single necrogenic dose of DENA (200 mg/kg, i.p) on day 21. Two groups received oral GE(108 or 216 mg/kg) daily for 28 days. Sera, liver, stomach and colon were obtained 7 days after DENA injection. Serumaspartate transaminase and alanine transaminase were detected as well as reduced glutathione (GSH), malondialdehyde,nitric oxide metabolites, interleukin 1β, tumor necrosis factor (TNF-α), alpha-fetoprotein (AFP) and nuclear factorerythroid2-related factor2 (Nrf2) in liver, stomach and colon. Histopathological studies and immunohistochemicalexamination of cyclooxygenase-2 (COX2) were conducted. Results: DENA induced elevation in liver function enzymeswith significant increase in oxidation and inflammation biomarkers and AFP while decreased levels of Nrf2 in liver,stomach and colon were detected. Histologically, DENA showed degenerative changes in hepatocytes and inflammatoryfoci. Inflammatory foci displayed increased expression of COX2 in immunohistochemical staining. GE-pretreatmentimproved liver function and restored normal GSH with significant mitigation of oxidative stress and inflammatorybiomarkers compared to DENA-treated group. AFP was reduced by GE in both doses, while Nrf2 increased significantly.Histology and immunostaining of hepatic COX-2 were remarkably improved in GE-treated groups in a dose dependentmanner. Conclusion: GE exerted a potential anti-proliferative activity against DENA in liver, stomach and colon viaNrf2 activation, whilst suppression of oxidation and inflammation.

AIM: The present study investigated the protective effect of the phytoestrogen, genistein (GEN), against (CP)-induced acute hepatotoxicity in rats.MATERIAL AND METHODS: Male adult rats were randomly assigned into five groups. Normal control group received the vehicles; CP group received a single dose of CP (200 mg/kg, i.p). The other three groups received subcutaneous GEN at doses of 0.5, 1 and 2 mg/kg/day, respectively, for 15 consecutive days prior CP injection. Sera and liver tissues were collected forty-eight hours after CP injection for assessment of liver function enzymes (ALT and AST) in rat sera, the hepatic oxidative/nitrosative biomarkers (GSH, MDA and NOx), hepatic interleukin-1β, and myeloperoxidase activity. Immunohistochemistry of cyclooxygenase-2 and histopathological examination of liver tissues were also conducted.RESULTS: The CP-induced acute liver damage was evidenced by elevated serum ALT and AST accompanied by increased hepatic oxidative stress and inflammatory biomarkers. Immunohistochemical outcomes revealed hepatic cyclooxygenase-2 expression in CP group with distortion of liver architecture. GEN-pretreatment significantly ameliorated the deterioration of liver function and exerted significant anti-oxidant and anti-inflammatory activity with a marked decline in hepatic cyclooxygenase-2 expression in a dose dependent-manner.CONCLUSION: The present study demonstrated that the antioxidant and anti-inflammatory activities of GEN might contribute to its protective effects against CP-induced liver damage.