Hydroxyethyl Starch

Doxorubicin (DOX), from the anthracycline family, is a widely utilized chemotherapy for various malignancies; however, its utility is limited due to the serious adverse reactions, particularly on the kidneys, primarily related to oxidative stress, inflammation, and apoptosis. Hesperetin (HES), the citrus fruit derivative, is a naturally occurring flavonoid. Previous studies underscored HES's protective efficacy against renal damage in several disorders in rodents through its proven antioxidant, antiapoptotic, and anti-inflammatory properties. This work explored the protecting role of HES against the nephrotoxic effects of DOX and the possible underlying mechanisms. Nephrotoxicity was induced in rats via administering six equal doses of DOX (3 mg/kg/week, i.p) for six consecutive weeks. The treated group received HES (50 mg/kg/day, p.o.) simultaneously with DOX. Rats' body and kidney weights, serum creatinine, blood urea nitrogen (BUN), and albumin were estimated. Kidney tissue was treated to assess redox status, histopathological, and immunohistochemical alterations. Compared to the controls, coadministration of HES with DOX significantly reduced the serum BUN and creatinine, elevated the serum albumin, amended the glomerular distortion and tubular epithelial degeneration, decreased collagen deposition, vascular congestion, and inflammatory cells in addition to the significant attenuation of inflammatory cytokines and proapoptotic markers. Our study is the first of its kind to underscore the HES's antioxidant, antiapoptotic, and anti-inflammatory activities in an experimental model of DOX-induced nephrotoxicity with emphasis on TNF-α, IL-1β, and IL-6 signaling pathway, rendering it as an effective therapeutic supplement that could alleviate the nephrotoxic effect of DOX.

This study explored the protective effects of hesperidin (HES) against ifosfamide (IFA)-induced nephrotoxicity in rats using biochemical, histopathological, and immunohistochemical techniques. The rats were administered IFA at a dose of 500 mg/kg body weight, followed by oral HES treatment at doses of 200 and 300 mg/kg body weight. The results demonstrated that HES significantly reduced IFA-induced increases in urea and creatinine levels, indicating improved kidney function. HES was shown to mitigate IFA-induced lipid peroxidation, likely due to its antioxidant properties, and to enhance the activities of key antioxidant enzymes, including catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx), as well as elevate glutathione (GSH) levels. Biochemical and immunohistochemical analyses further revealed that HES exhibited anti-inflammatory, antiapoptotic and anti-endoplasmic reticulum stress effects, suppressing the elevated levels of nuclear factor kappa-B (NF-κB), interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), Caspase-3, 6, 9, Bax, Apaf1, p53, serine/threonine-protein kinase/endoribonuclease inositol-requiring enzyme 1α (IRE1α), glucose-regulated protein 78 (GRP78), activating transcription factor 6 (ATF-6), and protein kinase R-like ER kinase (PERK), CHOP and alleviating level of Bcl-2 in IFA-exposed kidney tissue. Additionally, the immunohistochemical staining results for TIM-1 in rat kidney tissues showed minimal expression in the control and HES groups. However, the IFA-treated group exhibited a significant increase in TIM-1 expression. Co-administration of IFA with HES at 200 or 300 mg/kg resulted in a significant reduction in TIM-1 expression. In conclusion, these results demonstrate that HES efficiently alleviated kidney toxicity induced by IFA.