Hirsutidin Prevents Cisplatin-Evoked Renal Toxicity by Reducing Oxidative Stress/Inflammation and Restoring the Endogenous Enzymatic and Non-Enzymatic Level

Abstract

Recent research has shown that phytocomponents may be useful in the treatment of renal toxicity. This study was conducted to evaluate the renal disease hirsutidin in the paradigm of renal toxicity induced by cisplatin. Male Wistar rats were given cisplatin (3 mg/kg body weight/day, for 25 days, i.p.) to induce renal toxicity. Experimental rats were randomly allocated to four different groups: group I received saline, group II received cisplatin, group III received cisplatin + hirsutidin (10 mg/kg)and group IV (per se)received hirsutidin (10 m/kg)for 25 days. Various biochemical parameters were assessed, oxidative stress (superoxide dismutase (SOD), glutathione transferase (GSH), malonaldehyde (MDA) and catalase (CAT)), blood-chemistry parameters (blood urea nitrogen (BUN) and cholesterol), non-protein-nitrogenous components (uric acid, urea, and creatinine), and anti-inflammatory-tumor necrosis factor-α (TNF-α), interleukin-1β(IL-1β). IL-6 and nuclear factor-kB (NFκB) were evaluated and histopathology was conducted. Hirsutidin alleviated renal injury which was manifested by significantly diminished uric acid, urea, urine volume, creatinine, and BUN, compared to the cisplatin group. Hirsutidin restored the activities of several antioxidant enzyme parameters—MDA, CAT, GSH, and SOD. Additionally, there was a decline in the levels of inflammatory markers—TNF-α, IL-1β, IL-6, and NFκB—compared to the cisplatin group. The current research study shows that hirsutidin may act as a therapeutic agent for the treatment of nephrotoxicity induced by cisplatin.

Quillaja saponin mitigates methotrexate-provoked renal injury; insight into Nrf-2/Keap-1 pathway modulation with suppression of oxidative stress and inflammation

“…The right kidneys were fixed in 10% phosphate buffered formalin for histological assessments and immunohistochemical examinations of Bcl-2 and cleaved caspase-3 [ 25 ]. The left kidney in each group was divided into two parts; one part was homogenized (1/10 w/v) in ice-cold Tris–HCl buffer (0.1 M, pH 7.4) for the preparation of 10% tissue homogenate and kept in − 20 °C for biochemical assays (determination of oxidative stress and inflammatory markers) [ 26 ]. The second part was snap-frozen in liquid nitrogen and kept in − 80 °C for qRT-PCR studies (3 animals/group) for determination of Nrf-2and Keap-1 mRNA expression levels [ 27 ].…”