Effect of mitochondrial coenzyme-Q10 precursor solanesol in gentamicin-induced experimental nephrotoxicity: Evidence from restoration of ETC-complexes and histopathological alterations.

IF 2.9 4区 医学 Q2 PHARMACOLOGY & PHARMACY Pharmacology Research & Perspectives Pub Date : 2024-10-01 DOI:10.1002/prp2.70022
Minakshi Sangwan, Hema Chaudhary, Sidharth Mehan, Zuber Khan, Ammar A Bahauddin, Bandar D Alrehaili, Hossein M Elbadawy, Mohannad A Almikhlafi, Acharan S Narula, Reni Kalfin, Hanna Wanas
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Abstract

Nephrotoxicity occurs when the body is exposed to certain drugs or toxins. When kidney damage occurs, the kidney fails to eliminate excess urine and waste. Solanesol (C45H74O) is a tri-sesquiterpenoid alcohol first isolated from tobacco, and it is widely distributed in plants of the Solanaceae family. Solanesol (SNL) is an intermediate in the synthesis of coenzyme Q10 (CoQ10), an antioxidant which protects nerve cells. This study investigated the protective effect of SNL at doses of 30 and 60 mg/kg in gentamicin-induced nephrotoxicity in Wistar albino rats. Animals were distributed into six groups and administered 100 mg/kg gentamicin-intraperitoneal injection for 14 days. Biochemical assessments were performed on kidney homogenate, blood, and serum. Treatment with SNL was shown as lower serum levels of creatinine, blood urea nitrogen (BUN), thiobarbituric acid reactive substances (TBARS), and Tumor necrosis factor alpha)TNF-α ((p < .001). It also restored reduced glutathione (GSH) and mitochondrial complex enzymatic activity as protective measures against gentamicin-induced nephrotoxicity. SNL were shown to reduce inflammation and oxidative stress markers (p < .001). Histological findings furtherly augmented the protective effects of SNL. Long-term SNL therapy also restored mitochondrial electron transport chain complex enzymes, such as complex-I (p < .001). In conclusion, these findings suggest that SNL can represent a protective therapeutic option for drug-induced nephrotoxicity, a long-term adverse effect of aminoglycoside antibiotics such as gentamicin.

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线粒体辅酶-Q10 前体 Solanesol 对庆大霉素诱发的实验性肾毒性的影响:从 ETC 复合物的恢复和组织病理学改变中获得的证据。
当人体接触到某些药物或毒素时,就会产生肾毒性。当肾脏受损时,肾脏无法排出多余的尿液和废物。茄红素(Solanesol,C45H74O)是一种三倍半萜醇,最早从烟草中分离出来,广泛分布于茄科植物中。茄红素(SNL)是合成辅酶 Q10(CoQ10)的中间体,而辅酶 Q10 是一种保护神经细胞的抗氧化剂。本研究调查了剂量为 30 毫克/千克和 60 毫克/千克的 SNL 对庆大霉素诱导的 Wistar 白化大鼠肾毒性的保护作用。研究将大鼠分为六组,每组腹腔注射 100 毫克庆大霉素,连续 14 天。对肾脏匀浆、血液和血清进行了生化评估。接受 SNL 治疗的大鼠血清中肌酐、血尿素氮(BUN)、硫代巴比妥酸活性物质(TBARS)和肿瘤坏死因子α(TNF-α)的水平较低((p<0.05))。
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来源期刊
Pharmacology Research & Perspectives
Pharmacology Research & Perspectives Pharmacology, Toxicology and Pharmaceutics-General Pharmacology, Toxicology and Pharmaceutics
CiteScore
5.30
自引率
3.80%
发文量
120
审稿时长
20 weeks
期刊介绍: PR&P is jointly published by the American Society for Pharmacology and Experimental Therapeutics (ASPET), the British Pharmacological Society (BPS), and Wiley. PR&P is a bi-monthly open access journal that publishes a range of article types, including: target validation (preclinical papers that show a hypothesis is incorrect or papers on drugs that have failed in early clinical development); drug discovery reviews (strategy, hypotheses, and data resulting in a successful therapeutic drug); frontiers in translational medicine (drug and target validation for an unmet therapeutic need); pharmacological hypotheses (reviews that are oriented to inform a novel hypothesis); and replication studies (work that refutes key findings [failed replication] and work that validates key findings). PR&P publishes papers submitted directly to the journal and those referred from the journals of ASPET and the BPS
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