Rutin ameliorates carbon tetrachloride (CCl₄)-induced hepatorenal toxicity and hypogonadism in male rats

Abstract

Rutin, a food derived-polyphenolic bioflavonoid, has been acknowledged for several health benefits. This study aims to explore the ameliorative effects of rutin against carbon tetrachloride (CCl4) toxicity in male rats. Adult male rats were given either CCl4 (30% in olive oil, 3 ml/kg b.w. intraperitoneally) alone or in combination with rutin (70 mg/kg intragastrically) twice a week for 4 weeks. Our data showed that rutin mitigated CCl4 hepatorenal damage, as indicated by diagnostic markers (i.e., transaminases, alkaline phosphatase, total bilirubin, total protein, albumin, urea, uric acid and creatinine), and histopathological findings. In addition, CCl4 induced profound elevation of free radical generation and oxidative stress, as evidenced by increasing lipid peroxidation and reducing catalase, superoxide dismutase and glutathione peroxidase activities in liver, kidney and testicular tissues; these effects were suppressed by coexposure with rutin. Moreover, the increase in the levels of serum triglycerides, cholesterol, low-density lipoprotein cholesterol, and very-low-density lipoprotein cholesterol induced by CCl4 was effectively counteracted by rutin. The decrease in the level of high-density lipoprotein cholesterol in the CCl4 group was also counteracted by rutin treatment. Interestingly, the decreased levels of hormonal mediators associated with sperm production, including serum testosterone, luteinizing hormone and follicle-stimulating hormone, and the impaired sperm quality induced by CCl4 were reversed by rutin. Data from the current study clearly demonstrated that rutin supplementation could at least partly overcome CCl4-induced hepatotoxicity, nephrotoxicity and reproductive toxicity by antioxidant and antidyslipidemic effects.

Cross Talk Between TGF-β and JAK Expressions and Nepherotoxicity Induced by Tetrachloromethane: Role of Phytotherapy

“…Kidney sections of Tcmtreated group revealed changes in microanatomy. 20 The results of the current study were in accordance with that of Elsawy et al, 20 as Tcm exhibited an increase in serum creatinine, urea, and uric acid levels matched with the control values, and treatment with Mth or Tof or Csin alone or in combination improved all the previously measured parameters; the combination Figure 5. Anti-JAK immune-stained sections of kidney from rats (A) exposed to Tcm show strong immune positivity of tubular epithelium (arrow), while there are few glomeruli with positive reaction (star), and most of glomeruli show negative reaction (red triangle).…”

“…Kidney sections of Tcm-treated group revealed changes in microanatomy. 20 The results of the current study were in accordance with that of Elsawy et al, 20 as Tcm exhibited an increase in serum creatinine, urea, and uric acid levels matched with the control values, and treatment with Mth or Tof or Csin alone or in combination improved all the previously measured parameters; the combination regimen achieved the best renoprotective results. Moreover, Masson trichrome–stained kidney sections of rats that received Tcm showed increased deposition of fibrous tissue in the interstitium in between the tubules and the renal corpuscles, whereas administration of Mth or Tof or Csin diminished the abnormal fibrous tissue surrounding renal tubules.…”

Improvement of Testicular Steroidogenesis Using Flavonoids and Isoflavonoids for Prevention of Late-Onset Male Hypogonadism

“…Hesperidin glycoside, found in citrus fruits such as lemon and oranges, has been reported to reverse vanadium-induced decline in testosterone serum levels in male rats [80]. Hesperidin (16), a glycosylated form of hesperetin, (Figure 7) was also reported to reverse the decline of testosterone Recently, rutin (12) ( Figure 6), a glycosylated quercetin (7) found in citrus fruits, was shown to reverse the decreased levels of serum testosterone, LH, and FSH, as well as the impaired sperm quality, induced by carbon tetrachloride in male rats [73]. Carbon tetrachloride is an important environmental contaminant inducing male hypogonadism.…”

“…Recently, rutin (12) ( Figure 6), a glycosylated quercetin (7) found in citrus fruits, was shown to reverse the decreased levels of serum testosterone, LH, and FSH, as well as the impaired sperm quality, induced by carbon tetrachloride in male rats [73]. Carbon tetrachloride is an important environmental contaminant inducing male hypogonadism.…”

Polyherbal Medicine Divya Sarva-Kalp-Kwath Ameliorates Persistent Carbon Tetrachloride Induced Biochemical and Pathological Liver Impairments in Wistar Rats and in HepG2 Cells

“…Rotenoids (boeravinones) also possess anti-oxidant properties as they have been observed to have inhibitory effects on the production of cyclooxygenase (COX)-1, COX-2, and generation of cellular reactive oxygen species (Aviello et al, 2011;Bairwa et al, 2013;Son and Phan, 2014). Six plant metabolites further quantified using HPLC (caffeic acid, rutin, gallic acid, catechin, quercetin, and corilagin) have been studied extensively for their hepatoprotective activities against CCl 4 and drug exposures (Janbaz et al, 2004;Wang et al, 2014Wang et al, , 2019Elsawy et al, 2019;Ezzat et al, 2020). Owing to the different mode of action for the three plants per se and the presence of large variety of plant metabolites, it can be speculated that SKK probably functions at multiple levels in inhibiting CCl 4 induced hepatic injuries, i.e., through inhibition of oxidative stress, proinflammatory responses, and metabolizing enzymes CYPs (Khan et al, 2012;Wang et al, 2014;Ekstrand et al, 2015;Li et al, 2018).…”