Citrus aurantifolia (Chrism.) Swingle peel extract attenuate nephrotoxicity induced by doxorubicin

Abstract

Background: Doxorubicin (DOX) is an anthracycline antibiotic primarily utilized in the treatment of various solid tumors, including those affecting the cervix, ovaries, breasts, uterus, lungs, as well as certain blood cancers. However, the nephrotoxicity connected to DOX therapy restricts its clinical use. In an Ancient Chinese Medicine used Lime (Citrus. aurantifolia) Peel was employed to address cramps, colic pain, cold, and as an appetite stimulant. Lime is known as ''Zhi qiao'' in Traditional Chinese Medicine (TCM), in addition to its nephroprotective, antioxidant and immunostimulatory properties the peel had been noted for its effectiveness in regulating vital energy, used to treat cough, abdominal distention and constipation. Objective: The purpose of this research is to evaluate the potential protective effect of Citrus aurantifolia peel extract (CAPE) in alleviating the nephrotoxicity generated by doxorubicin (DOX) injection in rats. Methods: Thirty Wister albino rats were randomly and equally separated into six groups (n = 5), and they were treated as follows: group I received distilled water only (baseline), toxicant groups administered with 15 mg/kg, i.p. DOX, 24 h after, groups II, III IV, V and VI were treated with distilled water (negative control), Alpha lipoic acid, 150 mg/kg (positive control) and 100, 200 and 400 mg/kg of CAPE respectively, orally for seven days. Results: DOX caused kidney injury after a single intraperitoneal injection, as shown by substantial changes in kidney biomarkers, histological irregularities, and the reduction of antioxidant defense mechanisms (reduced glutathione, superoxide dismutase and catalase). CAPE treatment resulted in significant improvements in the amended renal biomarkers (urea, creatinine, albumin and uric acid), haematological parameters, antioxidative markers, and malondialdehyde. The present findings indicated that CAPE could reduce lipid peroxidation (LPO) and reactive oxygen species production, and observable histological improvements supported this result. Conclusion: Our results point out that CAPE is a potential therapeutic alternative for the prevention of DOX-related nephrotoxicity.

Keywords

• Nephrotoxicity
• Doxorubicin
• Oxidative stress
• Alpha lipoic acid
• Citrus aurantifolia