Open Access

ARTICLE

Boldine provides protective effect against nephrotoxicity induced by cisplatin in Wistar rats: Role of oxidative stress, inflammation and caspase-3

NERGIZ HACER TURGUT^1,*, HUSEYIN GUNGOR², MEHMET EKICI³, MUMIN ALPER ERDOGAN⁴, MEHMET ONDER KARAYIGIT⁵, HAKI KARA²

1 Department of Pharmacology, Faculty of Pharmacy, Izmir Katip Celebi University, Izmir, 35620, Turkey
2 Department of Pharmacology and Toxicology, Faculty of Veterinary Medicine, Cumhuriyet University, Sivas, 58140, Turkey
3 Department of Physiology, Faculty of Veterinary Medicine, Cumhuriyet University, Sivas, 58140, Turkey
4 Department of Physiology, Faculty of Medicine, Izmir Katip Celebi University, Izmir, 35620, Turkey
5 Department of Pathology, Faculty of Veterinary Medicine, Cumhuriyet University, Sivas, 58140, Turkey

* Corresponding Author: Nergiz Hacer Turgut,

BIOCELL 2022, 46(9), 2111-2122. https://doi.org/10.32604/biocell.2022.020383

Received 20 November 2021; Accepted 27 January 2022; Issue published 18 May 2022

Abstract

Side effects of cisplatin, especially dose-dependent nephrotoxicity, are major factors limiting its use in cancer. Boldine ((S)-2, 9-dihydroxy-1, 10-dimethoxy-aporphine) is a natural alkaloid known for its strong antioxidant activity present in leaves/bark of boldo tree (Peumus boldus Molina), a native tree in Chile. Here, we aimed to investigate the nephroprotective effect of boldine and its underlying mechanisms on cisplatin-induced rat renal injury. Thirty Wistar albino rats divided into 5 groups (Control, Cis, Bold.40, Cis + Bold.20, Cis + Bold.40 groups) were used. Rats received boldine (20 or 40 mg/kg/day), or vehicle (saline) intraperitoneal for 14 days and a single dose cisplatin (7 mg/kg, ip) was applied on the 10th day to induce nephrotoxicity. Rats and kidney tissue were weighed to determine kidney index. Blood urea nitrojen (BUN) and creatinine levels, the amount of thiobarbituric acid reactive substances (TBARS, an index of lipid peroxidation), superoxide dismutase (SOD), glutathione peroxidase (GPx) enzyme activities and tumor necrosis factor alpha (TNF-α) levels were measured and histopathologic examination was performed. Inducible nitric oxide synthase (iNOS) and caspase-3 expressions were detected immunohistochemically. Nephrotoxicity induced by cisplatin was apparent by elevated levels of BUN, creatinine, kidney index, TBARS and TNF-α, and decreased body weight, SOD and GPx enzyme levels. Pretreatment with boldine protected the renal function at both boldine doses by fixing the renal damage markers, oxidative stress, caspase-3 and iNOS expression. Histopathological findings supported biochemical findings. Taken together these findings indicate that boldine has promising protective effect against cisplatin nephrotoxicity by improving oxidative stress, inflammation, histopathological alterations and by alleviating caspase 3 expression.

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