ABSTRACT
Testicular dysfunction is a common adverse effect of cisplatin (CIS) administration as a chemotherapeutic drug. The current study has outlined the role of micro-RNAs (miR-155 and 34c) in CIS-induced testicular dysfunction and evaluated the protective effect of N-acetyl cysteine (NAC) and/or l-arginine (LA). Seven groups of Albino rats were used for this study. The control (C) group received physiological saline; the CIS group was injected CIS (7 mg/kg IP, once) on day 21 of the experiment; the NAC group was administered NAC (150 mg/kg intragastric, for 28 days); and the LA group was injected LA (50 mg/kg IP, for 28 days). NAC+CIS, LA+CIS, and NAC+LA+CIS groups received the above regime. CIS significantly reduced serum testosterone, LH, and FSH concentrations with decline of testicular enzyme activities. CIS caused significant elevation in testicular oxidative-stress biomarkers, inflammation-associated cytokines, and apoptosis markers, along with overexpression of miR-155 and low miR-34c expression. Additionally, marked testicular degenerative changes were observed in the examined histological section; a significant decrease in the expression of PCNA with significant increase in expressions of F4/80 and BAX was confirmed. The administration of NAC or LA upregulated testicular functions and improved histopathological and immunohistochemical changes as well as miRNA expression compared with the CIS-administered group. Rats receiving both NAC and LA showed a more significant ameliorative effect compared with groups receiving NAC or LA alone. In conclusion, NAC or LA showed an ameliorative effect against CIS-induced testicular toxicity and dysfunction through the regulation of antioxidant, anti-inflammatory, and antiapoptotic markers and via modulating miR-155 and miR-34c expression.
ABSTRACT
Astaxanthin (ASX), a red pigment belonging to carotenoids, has antioxidant activity and anti-oxidative stress effect. Atrazine (ATZ), a frequently used herbicide, whose degradation products are the cause for nephrosis and other oxidative stress associated diseases. This study was aimed to reveal the potential protective mechanism of astaxanthin against atrazine-induced nephrosis. Atrazine was orally given (250 mg/kg bw) to the mice along with astaxanthin (100 mg/kg bw) for 28 days. Serum biochemical indicators, oxidative stress biomarkers, ATPase activities, ion concentration, histomorphology, and various renal genes expression linked with apoptosis, Nrf2 signaling pathway, and aquaporins (AQPs) were assessed. It was found that serum creatinine (SCr), blood urea nitrogen (BUN), and MDA levels were significantly increased after the treatment of atrazine, whereas serum renal oxidative stress indicators like CAT, GSH, T-AOC, SOD decreased. Renal histopathology showed that atrazine significantly damaged renal tissues. The activities of Ca 2+-Mg 2+-ATPase were increased whereas Na +-K +-ATPase decreased significantly (P < 0.05). Moreover, results confirmed that the expression of AQPs, Nrf2, and apoptosis genes were also altered after atrazine administration. Interestingly, astaxanthin supplementation significantly (P < 0.05) improved atrazine-induced nephrotoxicity via decreasing SCr, BUN, oxidative stress, ionic homeostasis and reversing the changes in AQPs, Nrf2, and apoptosis gene expression. These findings collectively suggested that astaxanthin has strong potential ameliorative impact against atrazine induced nephrotoxicity.
ABSTRACT
Tilmicosin (TIL) is a semisynthetic macrolide antibiotic with a broad spectrum of activity derived from tylosin. TIL is effective in the treatment of bovine and ovine respiratory diseases caused by different microbes. In parallel, Rhodiola rosea (RHO) is a popular herbal remedy because of its anti-inflammatory and antioxidant qualities. The experiment lasted for 12 days. Depending on the experimental group, the animals received either distilled water or RHO root extract dissolved in distilled water for 12 days through a stomach tube, and the single subcutaneous injection on day 6 of the experiment of either 500 µL of 0.9% NaCl or TIL dissolved in 500 µL 0.9% NaCl. Samples and blood were collected for serum analysis, gene expression, and immunohistochemistry screening at liver and kidney levels. TIL injection increased serum levels of hepatic and renal markers (ALP, ALT, AST, TC, TG, creatinine, and urea) with decreased total proteins. In parallel, TIL induced hepatic and renal oxidative stress as there was an increase in malondialdehyde levels, with a decrease in catalase and reduced glutathione activities. Of interest, pre-administration of RHO inhibited TIL-induced increase in hepato-renal markers, decreased oxidative stress, and increased liver and kidney antioxidant activities. Quantitative RT-PCR showed that TIL increased the liver's HSP70 (heat shock protein), NFkB, and TNF-α mRNA expression. Moreover, TIL upregulated the expression of desmin, nestin, and vimentin expression in the kidney. The upregulated genes were decreased significantly in the protective group that received RHO. Serum inflammatory cytokines and genes of inflammatory markers were affected in liver tissues (HSP70, NFkB, and TNF-α) and kidney tissues (desmin, nestin, and vimentin)-TIL-induced hepatic vacuolation and congestion together with glomerular atrophy. The immunoreactivity of PCNA and HMGB1 was examined immunohistochemically. At cellular levels, PCNA was decreased while HMGB1 immunoreactivity was increased in TIL-injected rats, which was improved by pre-administration of RHO. RHO administration protected the altered changes in liver and renal histology. Current findings support the possible use of RHO to shield the liver and kidney from the negative effects of tilmicosin.
