Rhamnazin ameliorates 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin-evoked testicular toxicity by restoring biochemical, spermatogenic and histological profile in male albino rats.

2,3,7,8 tetrachlorodibenzo-p-dioxin (TCDD) is a potential environmental toxin that has the ability to affect male reproductive tract. Rhamnazin is a naturally present flavone that displays multiple medicinal properties. Therefore, the current study was designed to determine the mitigative role of rhamnazin against TCDD induced reproductive damage. 48 adult male albino rats were randomly separated into four groups: control, TCDD (10 µgkg-1), TCDD + rhamnazin (10 µgkg-1 + 5 mgkg-1 respectively) and rhamnazin (5 mgkg-1). The trial was conducted for 56 days. TCDD intoxication notably affected superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione reductase (GSR) and catalase (CAT) activities, besides reactive oxygen species (ROS) and malondialdehyde (MDA) concentrations were augmented. TCDD administration also lowered sperm motility, viability, sperm number, while it augmented the sperm morphological (tail, neck/midpiece and head) anomalies. Moreover, it decreased the levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH) and plasma testosterone. Moreover, TCDD reduced steroidogenic enzymes i.e., 17-beta hydroxysteroid dehydrogenase (17ß-HSD), steroidogenic acute regulatory protein (StAR) and 3-beta hydroxysteroid dehydrogenase (3ß-HSD) as well as B-cell lymphoma 2 (Bcl-2) expressions, but increased the expressions of Bcl-2-associated X protein (Bax) and cysteine-aspartic acid protease (Caspase-3). Furthermore, TCDD exposure also induced histopathological anomalies in testicular tissues. However, the supplementation of rhamnazin recovered all the mentioned damages in the testicles. The outcomes revealed that rhamnazin can ameliorate TCDD induced reproductive toxicity due to its anti-oxidant, anti-apoptotic and androgenic nature.

Eriodictyol attenuates Furan induced testicular toxicity in Rats: Role of oxidative stress, steroidogenic enzymes and apoptosis.

Furan (C4H4O) is a naturally occurring organic compound. It develops as a result of the thermal processing of food and stimulates critical impairments in male reproductive tract. Eriodictyol (Etyol) is a natural dietary flavonoid possessing diverse pharmacological potentials. The recent investigation was proposed to ascertain the ameliorative potential of eriodictyol against furan-instigated reproductive dysfunctions. Male rats (n = 48) were classified into 4 groups: untreated/control, furan (10 mg/kg), furan+ eriodictyol (10 mg/kg + 20 mg/kg) and eriodictyol (20 mg/kg). At the 56th day of the trial, the protective effects of eriodictyol were evaluated by assessing various parameters. Results of the study revealed that eriodictyol attenuated furan-induced testicular toxicity in the biochemical profile by increasing catalase (CAT), glutathione peroxidase (GPx), superoxide dismutase (SOD) along with glutathione reductase (GSR) activities, whereas reduced the reactive oxygen species (ROS) along with malondialdehyde (MDA) levels. It also restored the normal state of sperm motility, viability, the count of hypo-osmotic tail swelled sperm as well as epididymal sperm number along with reduced sperm anomalies (morphological) tail, mid-piece and head. Furthermore, it elevated the decreased levels of luteinizing hormone (LH), plasma testosterone and follicle-stimulating hormone (FSH) as well steroidogenic enzymes (17ß-HSD, StAR protein & 3ß-HSD) and testicular anti-apoptotic marker (Bcl-2) expression, whereas, down-regulating apoptotic markers (Bax & Caspase-3) expression. Eriodictyol treatment also effectively mitigated the histopathological damages. The outcomes of the current study provide fundamental insights into the ameliorative potential of eriodictyol against furan-instigated testicular toxicity.

Therapeutic effect of gossypetin against paraquat-induced testicular damage in male rats: a histological and biochemical study.

Paraquat (PQ) is an organic compound, which is commonly used as a herbicide in the agriculture sector, and it is also known to stimulate critical damages in the male reproductive system. Gossypetin (GPTN) is one of important members of the flavonoid family, which is an essential compound in flowers and calyx of Hibiscus sabdariffa with potential pharmacological properties. The current investigation was aimed to examine the ameliorative potential of GPTN against PQ-instigated testicular damages. Adult male Sprague-Dawley rats (n = 48) were distributed into four groups: control, PQ (5 mg/kg), PQ + GPTN (5 mg/kg + 30 mg/kg respectively), and GPTN (30 mg/kg). After 56 days of treatment, biochemical, spermatogenic indices, hormonal, steroidogenic, pro-or-anti-apoptotic, and histopathological parameters were estimated. PQ exposure disturbed the biochemical profile by reducing the activities of catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx), and glutathione reductase (GSR), while it increased the concentration of reactive oxygen species (ROS) and malondialdehyde (MDA) level. Furthermore, PQ exposure decreased the sperm motility, viability, number of hypo-osmotic tail swelled spermatozoa, and epididymal sperm count; additionally, it increased sperm morphological (head mid-piece and tail) abnormalities. Moreover, PQ lessened the follicle-stimulating hormone (FSH), luteinizing hormone (LH), and plasma testosterone levels. Besides, PQ-intoxication downregulated the gene expression of steroidogenic enzymes (StAR, 3ß-HSD, and 17ß-HSD) and anti-apoptotic marker (Bcl-2), whereas upregulated the gene expression of apoptotic markers (Bax and Caspase-3). PQ exposure led to histopathological damages in testicular tissues as well. Nonetheless, GPTN inverted all the illustrated impairments in testes. Taken together, GPTN could potently ameliorate PQ-induced reproductive dysfunctions due to its antioxidant, androgenic, and anti-apoptotic potential.

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

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-1ß (IL-1ß), 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.

Fisetin Attenuates Arsenic-Induced Hepatic Damage by Improving Biochemical, Inflammatory, Apoptotic, and Histological Profile: In Vivo and In Silico Approach.

Arsenic (As) is a toxic metalloid and human carcinogen that may cause hepatotoxicity. Fisetin (3, 3', 4', 7-tetrahydroxyflavone) is a phytoflavonoid, which shows diverse therapeutic activities. This study aimed to examine the remedial potential of fisetin against As-instigated hepatotoxicity in adult male rats. To accomplish this aim, albino rats (N = 48) were evenly classified into 4 groups: control group, As (10 mg/kg) group, fisetin (2.5 mg/kg) + As (10 mg/kg) group, and fisetin (2.5 mg/kg) group. After one month of treatment, biochemical assay, total protein content (TPC), hepatic serum enzymes, inflammatory as well as pro- or anti-apoptotic markers, and histopathological profile of hepatic tissues were estimated. As administration disordered the biochemical profile by decreasing activities of antioxidant enzymes i.e., catalase (CAT), superoxide dismutase (SOD), glutathione reductase (GSR), and glutathione (GSH) content while escalating the levels of reactive oxygen species (ROS), and thiobarbituric acid reactive substances (TBARS). TPC was also considerably reduced after exposure to As. Furthermore, As markedly raised the levels of liver serum enzymes such as aspartate transaminase (AST), alkaline phosphatase (ALP), and alanine transaminase (ALT) as well as the levels of inflammatory markers, i.e., nuclear factor- κB (NF-κB), tumor necrosis- α (TNF-α), interleukin-1ß (IL-1ß), interleukin-6 (IL-6), and cyclo-oxygenase-2 (COX-2) activity. Besides, it lowered the level of antiapoptotic markers (Bcl-2) and upregulated the levels of proapoptotic markers (Bax, Caspase-3, and Caspase-9). Additionally, As exposure led to histopathological damage in hepatic tissues. However, fisetin administration remarkably alleviated all the depicted hepatic damages. For further verification, the screening of several dock complexes was performed by using the GOLD 5.3.0 version. Based on docking fitness and GOLD score, the ranking order of receptor proteins with fisetin compound is superoxide dismutase, interleukin, aspartate aminotransferase, alkaline phosphatase, TNF-alpha, alanine transaminase, cyclo-oxygenase 2, antiapoptotic, and glutathione reductase. Out of these three receptor proteins superoxide dismutase, interleukin, and aspartate aminotransferase showed the best interaction with the fisetin compound. In vivo and in silico outcomes of the current study demonstrated that fisetin could potentially ameliorate As-instigated hepatotoxicity.

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

Background: Male reproductive damage is one of the most adverse side effects of doxorubicin (DOX). Isorhamnetin is a natural flavonoid, which displays remarkable antioxidant potential. Objective: The current research was designed to assess the protective effects of Isorhamnetin against DOX-instigated testicular damages. Methods: Adult male Wistar rats (n=32) were divided into 4 groups: control, DOX (3 mg/kg i.p. 3 doses each after 1 week), DOX + Isorhamnetin (3 mg/kg 3 doses each after 1 week +10 mg/kg i.p. daily for 28 days, respectively), and Isorhamnetin (10 mg/kg i.p. per day). After 28 days of treatment, biochemical, spermatogenic, steroidogenic, hormonal, proapoptotic, antiapoptotic, and histopathological parameters were estimated. Results: DOX exposure significantly decreased the activity of acid phosphatase, lactate dehydrogenase, and gamma-glutamyl transferase. Furthermore, DOX substantially decreased the activities of antioxidant enzymes, i.e. catalase, superoxide dismutase, glutathione reductase, and glutathione peroxidase along with protein content, whereas it increased the malondialdehyde level. It also reduced sperm progressive motility, viability, the number of hypoosmotic tail swelled spermatozoa, and epididymis sperm count and increased the sperm morphological anomalies (head, midpiece, and tail). Besides, it decreased the levels of follicle-stimulating hormone, luteinizing hormone, and plasma testosterone and lowered the expression of steroidogenic enzymes (3ß-hydroxysteroid dehydrogenase, 17ß-hydroxysteroid dehydrogenase, and steroidogenic acute regulatory protein) and testicular antiapoptotic marker (B-cell lymphoma 2) but increased the expression of proapoptotic markers (BCL2-associated X protein and caspase-3) along with histopathological impairments. However, isorhamnetin prevented all the damages caused by DOX. Conclusion: Conclusively, Isorhamnetin can be used as a powerful mitigating agent to avert DOX-induced testicular damages.

Pachypodol attenuates Perfluorooctane sulphonate-induced testicular damage by reducing oxidative stress.

Perfluorooctane sulfonate (PFOS) is an endocrine disruptor chemical (EDC) with potentially adverse effects on the male reproductive system. Pachypodol (5,4'-dihydroxy-3,7,3'-trimethoxyflavone) is a promising flavonoid isolated from Pogostemon cablin (Blanco) Benth that shows a broad range of pharmacological properties. However, the potential curative effects of pachypodol on testicular toxicity are not available until now. Therefore, this research was proposed to examine the efficiency of pachypodol against PFOS-induced testicular toxicity in adult male rats. The experiments were conducted on Sprague-Dawley rats (n = 48), which were equally distributed into four groups: control, PFOS (20 mg/kg), PFOS + Pachypodol (20 mg/kg + 10 mg/kg respectively), and Pachypodol (10 mg/kg). After 56 days of treatment, testes were excised by slaughtering rats, weighed, and stored till further analysis. The estimated parameters include biochemical markers, spermatogenic indices, hormonal and histopathological profiles. PFOS exposure disturbed the biochemical profile by altering the antioxidant/oxidant balance. For instance, it decreased the activities of catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx), and glutathione reductase (GSR) while increasing the concentration of reactive oxygen species (ROS) and level of thiobarbituric acid reactive substances (TBARS). PFOS intoxication also led to a notable decline in viability, motility, epididymal sperm count, and the number of HOS coiled-tail sperms, whereas the higher level of abnormality in the head, mid-piece, and tail of sperms were observed. Besides, it lowered luteinizing hormone (LH), follicle-stimulating hormone (FSH), and plasma testosterone. In addition, PFOS exposure led to histopathological damages in testicles. However, pachypodol treatment potently alleviated all the illustrated impairments in testes. Conclusively, our results demonstrate the promising free-radical scavenging activity of pachypodol, a novel phytochemical, against the PFOS-instigated testicular dysfunctions.

Protective effect of myricetin on nonylphenol-induced testicular toxicity: biochemical, steroidogenic, hormonal, spermatogenic, and histological-based evidences.

Nonylphenol (NP) is an environmental contaminant, which induces testicular toxicity through oxidative stress. Myricetin (MYR) is a naturally occurring flavonol having powerful antioxidant activity. The current research was planned to examine the ameliorative role of MYR against NP-induced testicular damage. A total of 24 adult male Sprague-Dawley rats were randomly divided into 4 equivalent groups: control (0.1% DMSO), NP group (50 mg kg-1), NP + MYR group (50 mg kg-1; 100 mg kg-1), and MYR-treated group (100 mg kg-1). NP administration significantly (p < 0.05) decreased the activity of antioxidant enzymes, including catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione reductase (GSR), and protein content while significantly (p < 0.05) elevating the thiobarbituric acid reactive substances (TBARS) and reactive oxygen species (ROS) levels. Additionally, NP significantly (p < 0.05) reduced the sperm motility, gene expression of testicular steroidogenic enzymes (3ß-HSD, 3ß-hydroxysteroid dehydrogenase; 17ß-HSD, 17ß-hydroxysteroid dehydrogenase; StAR, steroidogenic-acute regulatory protein), level of luteinizing hormone (LH), follicle-stimulating hormone (FSH), plasma testosterone, and daily sperm production (DSP). On the other hand, it raised the testicular cholesterol, dead sperms, and head, midpiece, and tail abnormalities along with abnormal histomorphometry. However, MYR remarkably abrogated NP-induced damages. In conclusion, the outcomes of the study suggest that MYR can effectively alleviate the NP-induced oxidative stress and testicular damages.