Ameliorative effects of morin on cisplatin-induced toxicity in renal mitochondria isolated from rats

Ijaz, Muhammad Umar; Shahzadi, Sabahat; Zahra, Zartash; Samad, Abdul; Ehsan, Nazia; Afsar, Tayyaba; Almajwal, Ali; Aldisi, Dara; Abulmeaty, Mahmoud M. A.; Razak, Suhail

doi:10.1016/j.jksus.2021.101655

Cited by 6 publications

(4 citation statements)

References 35 publications

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“…However, in the present study, co-treatment of GM with CAS reversed the enzyme's activity. Our results are in agreement with the study conducted by Ijaz et al (2021) in which morin, another member of flavonoid family improved the activities of TCA cycle enzyme. Decreased production of ROS might be responsible for the reestablishment of enzymatic status.…”

Section: Discussionsupporting

confidence: 93%

Study on the Effects of Casticin Against Gm-Induced Oxidative Damage, Serum Chemistry and Mitochondria in Rats

2023

THE JAPS

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Gentamicin (GM) is an important aminoglycoside antibiotic to treat different infections caused by gram-negative bacteria. Mitochondrial dysfunction is considered as a key factor in the pathogenesis of renal disorders, and an important consequence of GM-induced nephrotoxicity that results in structural and functional alteration. Casticin (CAS) is a potential phytochemical having various pharmacological properties. The current investigation was formulated to ascertain the protective effects of CAS on GM induced mitochondrial dysfunction in kidney of rats. For this study, mature Sprague Dawley rats (n=48), weighing 200 ± 20g were used and divided into four groups (n=12) using a completely randomized design (CRD); Group 1 (control group), Group 2 (GM dose, 80 mgkg -1 b. wt i.p), Group 3 (80 mg/kg GM (i.p) and 50 mgkg -1 b.wt of CAS orally) and Group 4 (CAS 50 mgkg -1 b.wt orally). All rats were treated for ten days continuously. Our finding showed that GM administration significantly increased the concentration of urea and creatinine; however, creatinine clearance was reduced. GM treatment increased the level of mitochondrial reactive oxygen species (ROS) and lipid peroxidation, while the activity of glutathione, catalase, superoxide dismutase and glutathione peroxidase were decreased. Mitochondrial tricarboxylic acid (TCA) cycle enzymes (succinate dehydrogenase, isocitrate dehydrogenase, malate dehydrogenase and alpha-ketoglutarate dehydrogenase) activities were decreased after GM exposure. In addition, mitochondrial electron transport chain (ETC) enzymes, i.e., NADH dehydrogenase, succinate-dehydrogenase, succinic-coenzyme Q and cytochrome c-oxidase activities were reduced followed by GM administration. GM administration decreased mitochondrial membrane potential (ΔΨm) while significantly induced histological damage. However, treatment of CAS abrogated the damaging effects of GM in isolated renal mitochondria. Therefore, the present study demonstrated that CAS exhibits palliative effects against GM-induced renal mitochondrial impairment in the rats.

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Section: Discussionsupporting

confidence: 93%

Study on the Effects of Casticin Against Gm-Induced Oxidative Damage, Serum Chemistry and Mitochondria in Rats

2023

THE JAPS

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“…Decreased production of ROS might be responsible for the restoration of enzymatic activities. Outcomes of the study are further in compliance with the findings of Ijaz et al, 79 in which morin, a close relative of HBN, significantly reversed the activities of mitochondrial enzymes potentially due to its antioxidant activity.…”

Section: Discussionsupporting

confidence: 85%

Ameliorative effect of herbacetin against cyclophosphamide-induced nephrotoxicity in rats via attenuation of oxidative stress, inflammation, apoptosis and mitochondrial dysfunction

et al. 2022

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Herbacetin (HBN) is a glycosylated flavonoid, which possesses numerous pharmacological properties. Cyclophosphamide (CYC) is a chemotherapeutic drug that adversely affects the kidneys. The present investigation aimed to evaluate the curative potential of HBN against CYC-induced nephrotoxicity. Sprague Dawley rats ( n = 48) were randomly divided into four groups: control (0.1% DMSO + food), CYC (150 mg/kg b.wt.), CYC+HBN (150 + 40 mg/kg b.wt.), and HBN (40mg/kg b.wt.). CYC treatment significantly decreased the activities of antioxidant enzymes such as catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx), and glutathione reductase (GSR) while elevating the concentration of reactive oxygen species (ROS) and malondialdehyde (MDA). Treatment with HBN significantly recovered the activity of CAT, SOD, GPx, and GSR while reducing the concentrations of ROS and MDA. Moreover, an increase in the level of renal functional markers, including Urea, creatinine, kidney injury molecule-1 (KIM-1), and neutrophil gelatinase-associated lipocalin (NGAL), and a decrease in creatinine clearance after CYC administration was recovered to control values by HBN treatment. Furthermore, HBN treatment normalized the increased levels of inflammatory markers such as nuclear factor kappa-B (NF-κB), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) after CYC administration. Besides, HBN administration increased the expression of anti-apoptotic markers (Bcl-2) while decreasing the apoptotic markers (Bax and Caspase-3). Furthermore, HBN decreased the activities of tricarboxylic acid (TCA) cycle enzymes (ICDH, αKGDH, SDH, and MDH) as well as renal mitochondrial respiratory-chain complexes (I-IV) and repolarized mitochondrial membrane potential (ΔΨm). Additionally, HBN administration significantly protected against renal histological damage induced by CYC. In conclusion, CYC-induced toxicity was effectively ameliorated by the HBN administration. These results indicate that HBN might be considered as a potential protective agent against nephrotoxicity. The observed protection may be due to its antioxidant, anti-inflammatory, and anti-apoptotic potential.

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“…It has shown that CP injection has attenuated the energetic function of mitochondria significantly. The results herein are in harmony with previous reports of Ijaz et al, where CP injection has disrupted mitochondrial function as observed by reduced (ETC) enzymes, as succinic-coenzyme Q, NADH dehydrogenase, cytochrome c-oxidase, and mitochondriaΔΨm 30. Similarly, Yuan et al, reported low ATP and decline in mitochondrial ΔΨm upon CP injection 31.…”

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confidence: 92%

The cardioprotective effect of human glucagon‐like peptide‐1 receptor agonist (semaglutide) on cisplatin‐induced cardiotoxicity in rats: Targeting mitochondrial functions, dynamics, biogenesis, and redox status pathways

Atef

Hafez

El-Deeb

et al. 2023

Cell Biochemistry & Function

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The cardiotoxic effect of chemotherapeutic agents as cisplatin has become a major issue recently. Interference with mitochondrial dynamics, biogenesis, redox status, and apoptosis are the most possible underlying mechanisms. Semaglutide is a human glucagon‐like peptide‐1 receptor agonist (GLP‐1R), which is used primarily for the treatment of DM. Various recent studies have investigated (GLP‐1R) role in cardiovascular diseases due to antiapoptotic and antioxidant effects. The current study aimed to investigate the curative role of semaglutide's against cisplatin‐ induced cardiotoxicity and its relation to mitochondrial functions, dynamics, biogenesis, apoptosis, and redox status pathways. The study included 30 male rats divided into three groups: control, cisplatin‐induced cardiotoxicity, and cisplatin‐induced cardiotoxicity treated with semaglutide. At the end of the experiment heart index, serum cardiotoxicity markers, SOD, GPX activities and H2O2 level were estimated. Mitochondrial transmembrane potential, complex I and citrate synthase enzyme activities, ATP level, Mfn2 in addition to PGC‐1 α levels were assessed as biogenesis markers. Mitophagy markers PINK1 and Parkin mRNA gene expression were estimated. Histopathological examination of cardiac muscles of all studied groups and immunoassay of P53 and caspase 3 in cardiac tissue were examined to assess apoptosis. Cisplatin has disturbed mitochondrial function and dynamics, dysregulate redox status and induced mitophagy and apoptosis, in the other hand semaglutide treatment has normalized dysregulated mitochondrial function and dynamics, redox status and suppressed mitophagy and apoptosis. Semaglutide has ameliorative effect against cisplatin‐ induced cardiotoxicity via modulation of mitochondrial functions, dynamics, biogenesis, apoptosis, and redox status pathways.

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Ameliorative effects of morin on cisplatin-induced toxicity in renal mitochondria isolated from rats

Cited by 6 publications

References 35 publications

Study on the Effects of Casticin Against Gm-Induced Oxidative Damage, Serum Chemistry and Mitochondria in Rats

Study on the Effects of Casticin Against Gm-Induced Oxidative Damage, Serum Chemistry and Mitochondria in Rats

Ameliorative effect of herbacetin against cyclophosphamide-induced nephrotoxicity in rats via attenuation of oxidative stress, inflammation, apoptosis and mitochondrial dysfunction

The cardioprotective effect of human glucagon‐like peptide‐1 receptor agonist (semaglutide) on cisplatin‐induced cardiotoxicity in rats: Targeting mitochondrial functions, dynamics, biogenesis, and redox status pathways

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