Isorhamnetin: a flavonoid, attenuated doxorubicin-induced testicular injury via regulation of steroidogenic enzymes and apoptotic signaling gene expression in male rats

Mustafa, Shama; Ijaz, Muhammad Umar; Ain, Qurat Ul; Afsar, Tayyaba; Almajwal, Ali; Shafique, Huma; Razak, Suhail

doi:10.1093/toxres/tfac024

Cited by 11 publications

(6 citation statements)

References 62 publications

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“…Furthermore, the decrease in the quantity and quality of sperm of HCB alone rats may be linked to the diminution of testosterone that is crucial to sperm viability and spermatogenesis. 46,47 The detrimental effects of HCB on the quality and quantity of sperm in rats in the study correspond to the earlier reports of Batiri et al 8 However, administration of THY to HCB rats ameliorated the toxic impact of HCB suggesting the positive influence of THY on the epididymal and testicular wellbeing. Our results similar to the previous report of Guvec et al 19…”

Section: Discussionsupporting

confidence: 89%

Thymol co-administration abrogates hexachlorobenzene-induced reproductive toxicities in male rats

2023

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This present study was designed to investigate ameliorating potential of thymol (THY) on hexachlorobenzene (HBC)-induced epididymal and testicular toxicities in adult male rats. Forty adult male rats were orally treated by gavage daily for 28 consecutive days and divided into four groups; control group administered with corn oil, HBC-treated group (16 mg/kg b. wt), thymol-treated group (30 mg/kg b. wt), and HBC + THY-treated group. The results revealed that HBC exposure caused a significant decrease in the body weight change, organ weights, sperm functional parameters, serum testosterone level with widespread histological abnormalities. Furthermore, HBC-treated rats showed increased in the serum levels of luteinizing hormone (LH) and follicle stimulating hormone (FSH), epididymal and testicular myeloperoxidase activity, tumor necrosis-α, interleukin-1β level and caspase-3 activity, induced oxidative damage as evidenced by elevated malondialdehyde (MDA), reactive oxygen species (RONS) levels and significant reduction in antioxidant enzyme activities and reduced glutathione (GSH). However, co-treatment of THY with HBC alleviated the HBC-induced epididymal and testicular toxicities. Our findings revealed that HBC acts as a reproductive toxicant in rats and thymol could be a potential remedial agent for HBC-induced reproductive toxicity.

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Section: Discussionsupporting

confidence: 89%

Thymol co-administration abrogates hexachlorobenzene-induced reproductive toxicities in male rats

2023

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“…Imbalance in ROS and antioxidant defense systems leads to OS, which ultimately results in oxidative damage. 48,49 An increase in free radicals causes overproduction of MDA, which is an indicator of lipid peroxidation. 50 LP is commonly known as a marker of OS and antioxidant status.…”

Section: Discussionmentioning

confidence: 99%

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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“…Similarly, pretreatment of mice with isorhamnetin produced dose dependency and a significant increase in catalase activity in the hippocampus (2.41 folds) and prefrontal cortex (2.63 folds) when compared with vehicle-scopolamine-treated group (Ishola et al, 2019). Mustafa et al (2022) studied the effect of isorhamnetin in doxorubicin-induced testicular injury model in male rats. Doxorubicin-induced oxidative stress was significantly reduced by isorhamnetin treatment due to the increase in SOD (by 2.39 folds) and catalase (by 1.72 folds) activities compared to doxorubicin-treated control (Mustafa et al, 2022).…”

Section: Antioxidant Activitymentioning

confidence: 99%

“…Mustafa et al (2022) studied the effect of isorhamnetin in doxorubicin-induced testicular injury model in male rats. Doxorubicin-induced oxidative stress was significantly reduced by isorhamnetin treatment due to the increase in SOD (by 2.39 folds) and catalase (by 1.72 folds) activities compared to doxorubicin-treated control (Mustafa et al, 2022).…”

Section: Antioxidant Activitymentioning

confidence: 99%

“…The preservation and accumulation of cholesterol-rich apoB-containing lipoproteins within the arterial intima at plaque-prone sites are key pathophysiological mechanisms in the establishment of ASCVD (Ference et al, 2017). Over 200 studies including more than 2 million individuals and over 150,000 cardiovascular events demonstrated a dose-dependent, log-linear relationship between LDL level and ASCVD threat (Ference et al, 2017;Lewington et al, 2007;Nordestgaard et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

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Isorhamnetin decreased the expression of HMG-CoA reductase and increased LDL receptors in HepG2 cells

Rayyes¹,

Abbas²,

Obeidat³

et al. 2023

J App Pharm Sc

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Isorhamnetin is a flavonoid present in many plants. In a previous in vivo study, isorhamnetin lowered serum cholesterol of rats fed high-cholesterol diet. However, its mechanism of action was not investigated. In the present work, the mechanism of its hypocholesterolemic effect was studied. The expression of 3-hydroxy-3-methylglutaryl-CoA reductase (HMG-CoA reductase) and low-density lipoprotein receptor (LDLR) genes and proteins was studied in HepG2 liver cancer cell line by polymerase chain reaction, western blot, and indirect enzyme-linked immunosorbent assay as well as its antioxidant activity. sorhamnetin had an IC 50 of 100, 53, and 40 µM at 24, 48, and 72 hours, respectively, in HepG2 cells. Isorhamnetin downregulated HMG-CoA reductase gene expression significantly. Also, all tested doses of isorhamnetin downregulated LDLR expression and produced no change in membranous LDLR protein expression. In cell lysate, LDLR was increased by all studied concentrations of isorhamnetin. Isorhamnetin (100 µM) decreased intracellular HMG-CoA reductase compared to vehicle-treated control. Furthermore, isorhamnetin increased superoxide dismutase activity and reduced H 2 O 2 level, due to catalase activity. Isorhamnetin reduced HMG-CoA reductase gene expression and increased total LDLR and exerted pronounced antioxidant action.

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Isorhamnetin: a flavonoid, attenuated doxorubicin-induced testicular injury via regulation of steroidogenic enzymes and apoptotic signaling gene expression in male rats

Cited by 11 publications

References 62 publications

Thymol co-administration abrogates hexachlorobenzene-induced reproductive toxicities in male rats

Thymol co-administration abrogates hexachlorobenzene-induced reproductive toxicities in male rats

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

Isorhamnetin decreased the expression of HMG-CoA reductase and increased LDL receptors in HepG2 cells

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