Naringin from sweet orange peel improves testicular function in high fat diet-induced diabetic rats by modulating xanthine oxidase/uric acid signaling and maintaining redox balance.

BACKGROUND: Type 2 diabetes mellitus (T2DM) is a metabolic disorder affecting many organs, including the testis. Naringin from orange peel extract (OPE) is a flavanone with fertility-enhancing properties. Hence, this study was designed to establish the effect of naringin on T2DM-induced testicular dysfunction. Thirty male (30) Wistar rats were randomized into five groups control, diabetes, diabetes + naringin, diabetes + OPE, and diabetes + metformin. The administrations were via the oral route and lasted for 28 days. RESULTS: Naringin ameliorated T2DM-induced increase in FBS and decrease in serum insulin. It also abrogated T2DM-induced decrease in sperm quality, gonadotropin-releasing hormone, luteinizing hormone, follicle-stimulating hormone, testosterone, estradiol, prolactin, catalase, superoxide dismutase, and total antioxidant capacity. Furthermore, naringin prevented a T2DM-induced increase in malonaldehyde, tumor necrosis factor-alpha, C-reactive protein, xanthine oxidase (XO), and uric acid (UA), it was accompanied by the restoration of normal testicular histoarchitecture. CONCLUSIONS: Naringin prevented T2DM-induced testicular dysfunction by modulating XO/UA and restoring redox balance. Also, while the animals treated with OPE exhibited better ameliorative effects than their counterparts treated with naringin, the findings from this study showed that naringin would be a promising supplement for treating T2DM-induced male infertility.

Disruptive consequences of monosodium glutamate on male reproductive function: A review.

Monosodium glutamate (MSG) is one of the most extensively used flavour enhancers worldwide. Although it is widely regarded as a safe food additive with no recommended daily dosage, its over-consumption has been associated with notably pathophysiological events in various tissues and organs of the body. Previous studies have reported of the neuro- cardio- and hepato- toxic effects of its excessive exposure. Moreover, the food additive instigates metabolic dysfunction. It has been established that MSG damages male reproductive accessory organs like prostate glands and epididymis. In addition, it impairs serum enzymatic activities and serum levels of testosterone, gonadotropin-releasing hormone, luteinizing hormone and cholesterol. Reduced sperm count, sperm motility, sperm morphology, and sperm viability, imbalances in male reproductive hormones, alongside alteration in the histoarchitecture of the testes and other male reproductive tissues have also been connected with excessive exposure to MSG. Literature reports affirm the link between the over-consumption of MSG and reproductive organ weight and male sexual behaviour. This review article addresses the multi-systemic effects of exposure to MSG and the possible mechanism of action of the compound with a focus on the negative implications of the food additive on male reproductive functions and the possible role of natural antioxidants in male reproductive functions. carefully selected keywords were used during the literature search to gather credible and up-to-date information about the subject matter.

Omega-3 fatty acid ameliorates bisphenol F-induced testicular toxicity by modulating Nrf2/NFkB pathway and apoptotic signaling.

Introduction: Bisphenol F (BPF) has been shown to disrupt testicular functions via perturbation of testicular redox balance, while omega-3 fatty acid (O3FA) has been established to exert antioxidant and anti-inflammatory activities. Therefore, this study focused on the role and associated molecular mechanism of O3FA in BPF-induced testicular dysfunction in male Wistar rats. Methods: Twenty-four (24) rats were randomly grouped after two weeks of acclimatization into four (4) groups (n=6/group); the vehicle-treated control group, BPF treated group received 30 mg/kg of BPF, and the intervention groups received 30 mg/kg BPF + 100 mg/kg O3FA (BPF+O3FA-L) and 30 mg/kg BPF + 300 mg/kg of O3FA (BPF+O3FA-H). All treatment lasted for 28 days. Results: Low and high doses of O3FA ameliorated BPF-impaired sperm quality, and induced hormonal imbalance, accompanied by a distortion in testicular histology and elevated testicular injury markers. Furthermore, co-administration of BPF with both doses of O3FA blunted BPF-induced redox imbalance, inflammatory response, and apoptosis. Discussions: In conclusion, our present findings show that O3FA improves testicular functions in BPF-treated rats by improving sperm quality and reproductive hormones via the maintenance of testicular redox balance.

In vivo exposure to bisphenol F induces oxidative testicular toxicity: role of Erß and p53/Bcl-2 signaling pathway.

Introduction: Bisphenol F (BPF), an alternative to bisphenol A has been implicated as a gonadotoxic substance. BPF has been shown to induce hormonal imbalance and testicular oxidative damage. However, the mechanism associated with BPF-induced testicular toxicity has not been fully explored. This study was designed to explore the role of tumor protein (p53)/ B-cell lymphoma 2 (BCl-2) signaling and oestrogen receptor beta (Erß) in BPF-induced testicular toxicity. Methods: Male Wistar rats were randomized into control (Cntrl), BPF-treated (10, 30, and 50 mg/kg for low dose (BPF-L), medium dose (BPF-M), and high dose (BPF-H) respectively), and BPF-treated recovery (Cntrl-R, BPF-L-R, BPF-M-R, and BPF-H-R). The administration was via gavage and lasted for 28 days and the animals in the recovery groups were allowed 28-days exposure free period for recovery from BPF exposure. Results: BPF resulted in the distortion of the testicular histoarchitecture, which was accompanied by a significant rise in testicular gamma-lutamyl transferase and lactate dehydrogenase activities but a decline in sorbitol dehydrogenase activities. Also, BPF caused a significant reduction in plasma gonadotropin-releasing hormone, luteinising hormone, follicle-stimulating hormone, and testosterone, which was associated with the downregulation of testicular 3beta-hydroxysteroid dehydrogenase and 17beta-hydroxysteroid dehydrogenase activities. Furthermore, BPF induced testicular inflammation, redox imbalance, and apoptosis, accompanied by distortion in p53/BCl-2 signaling and overexpression of Erß. Again, the observed toxic effects of BPF were dose-dependent and not completely reversed by BPF cessation. Discussion: Bisphenol F induced gonadotoxicity by distorting p53/BCl2 signaling and the expression of Erß. These observed alterations were not completely reversed after the cessation of BPF exposure.

Mechanism associated with changes in male reproductive functions during ageing process.

Ageing is a natural process with physiological changes in different body parts and has been associated with decreased reproductive capacity. Factors such as imbalance in the antioxidant defence system, vascular diseases, diabetes mellitus, accessory reproductive glands infection, obesity as well as buildup of toxic substances play a role in age-related male reproductive malfunction. Age is inversely proportional to volume of semen, sperm count, sperm progressive motility, sperm viability, normal sperm morphology. The observed negative correlation between ageing and semen indices contributes to male infertility and reproductive decline. Normal levels of ROS, plays crucial role in facilitating sperm function, such as capacitation, hyper-activation, acrosome reaction as well as sperm-oocyte fusion; however, a substantial elevation in the endogenous level of ROS, especially in reproductive tissues, usually instigates destruction of sperm cells and heightened male infertility. Contrarily, antioxidants, such as vitamins C and E, beta-carotene, and micronutrients like zinc and folate, have been found by researchers to facilitate normal semen quality and male reproductive function. Furthermore, the role of hormonal imbalance as a result of the compromised hypothalamic-pituitary-gonadal axis, Sertoli and Leydig cells disorder, and nitric oxide-medicated erectile dysfunction during ageing cannot be undermined.

Dietary Supplementation with D-Ribose-L-Cysteine Prevents Hepatic Stress and Pro-Inflammatory Responses in Male Wistar Rats Fed a High-Fructose High-Fat Diet.

Diets rich in fats and fructose are associated with the pathogenesis of oxidative stress-induced non-alcoholic fatty liver disease. Therefore, we investigated the effect of D-ribose-L-cysteine (DRLC) in high-fructose high-fat (HFHF) diet-fed rats. Twenty rats (n = 5), divided into four groups, were simultaneously exposed to HFHF and/or DRLC (250 mg/kg) orally during the 8 weeks of the study. Results showed that HFHF precipitated pro-inflammation and selective disruption of the oxidative stress markers. There were significant decreases in the level of antioxidants such as superoxide dismutase (SOD), glutathione peroxidase (GPX), total antioxidant capacity (TAC), hepatic SOD and GPX. Significant increases in serum levels of uric acid (UA), tumour necrosis factor-alpha (TNF-α), C-reactive protein (CRP) and hepatic Xanthine oxidase (XO) were observed in the HFHF compared to the control. In the HFHF + DRLC group, oxidative stress was mitigated due to differences in serum levels of SOD, GPX, TAC, TNF-α, liver SOD, and XO relative to control. The administration of DRLC alone caused significant reductions in malondialdehyde, UA and CRP and a significant increase in SOD compared to the control. DRLC prevents hepatic and systemic oxidative stress and pro-inflammatory events in HFHF diet-fed rats.

D-ribose-L-cysteine prevents oxidative stress and cardiometabolic syndrome in high fructose high fat diet fed rats.

Cardiometabolic syndrome has been linked with dietary modification. Therefore, we investigated the effects of D-ribose-L-cysteine (DRLC) in rats fed with high fructose high fat (HFHF) diet. Twenty rats (n = 5), divided into 4 groups were concurrently exposed to HFHF and/or DRLC (250 mg/kg, p.o) during the 8 weeks study. The result showed that compared to control group, HFHF group had significant impairment in lipid and glucose homeostasis, increased cardiac xanthine oxidase, systolic blood pressure, heart rate, %body weight change and fluid intake. Also, there were significant reductions in HDL-C, cardiac (GPX, NO&GGT), feed intake and relative heart weight in the latter, relative to the former. However, there were no significant differences in most of the observed physical and biochemical changes in HFHF + DRLC group compared to control. DRLC alone did not disrupt the level of biomarkers. Conclusively, DRLC prevented the manifestation of oxidative stress and cardiometabolic syndrome in HFHF-diet fed rats.

Elevated, sustained, and yet reversible biotoxicity effects of lead on cessation of exposure: Melatonin is a potent therapeutic option.

Melatonin (Mel) is known to prevent and mitigate lead (Pb)-induced gonadotoxicity. However, there is no report in literature on the endogenous levels of different biomarkers after the cessation of Pb exposure, with or without treatment with Mel. Fifty adult male Wistar rats were divided into five groups (N = 10), which included control ((vehicle (normal saline) - treated) - 0.1 ml/day); lead chloride (PbCl2) untreated (3 weeks vehicle + 3 weeks Pb); Pb recovery (3 weeks Pb + 3 weeks vehicle); Pb + Mel (3 weeks Pb + 3 weeks Mel); and Mel (3 weeks vehicle + 3 weeks Mel) groups. Pb and Mel were administered at 50 and 10 mg/kg B.W. (p.o.), respectively. The results showed that Pb caused significant decreases in total bilirubin (TB), phospholipids (PLP), superoxide dismutase (SOD), catalase (CAT), and total antioxidant capacity (TAC), but significant elevations in alkaline phosphatase (ALP), aspartate aminotransferase (AST), triglyceride (TG), and malondialdehyde (MDA). Although the adverse effects of Pb on TB, ALP, AST, SOD, MDA, and TAC were sustained after the cessation of exposure, a reversal was observed in total cholesterol (TC), TG, PLP, CAT, and c-reactive protein (CRP) results. Nevertheless, the detrimental effects of Pb on alanine aminotransferase (ALT), albumin, and globulin were only expressed post-exposure. Treatment with Mel caused no significant effect on TB and albumin levels. However, unlike TAC and CRP, the hormone significantly reduced ALP, AST, ALT, TC, low-density lipoprotein cholesterol, PLP, SOD, CAT, MDA, and globulin to levels comparable to the control group. In conclusion, following the cessation of Pb exposure, alterations in physiological balance could be elevated, sustained, or reversible. However, Mel enhanced the reestablishment homeostatic status after Pb administration.

Investigation of the effects of dietary modification in experimental obesity: low dose of virgin coconut oil has a potent therapeutic value.

There is no report in literature on possible physiological changes that accompany dietary modification in obese condition. Moreover, there is no conclusive evidence on the optimal amount of virgin coconut oil (VCO) that could be of health benefit, although it is known to enhance lipid metabolism. Therefore, we investigated the antiobesitogenic action of graded doses of VCO (200, 400 and 600 mg/kg) in obese rats fed with normo/hyper-lipidaemic diet. Sixty rats (n = 10) were divided into 6 groups and treated as follows: the control and high fat diet (HFD) groups were administered normal saline (0.1 mL/day, p.o.) during the last four weeks of the study, and were fed with normal and HFD respectively throughout the twenty weeks duration of the experiment. Groups 3-6 were fed with HFD for 16 weeks, then normal diet during the next 4 weeks. While group - 3 received saline (0.1 mL/day, p.o.) during the last four weeks, groups 4-6 received graded doses of VCO. The results showed that HFD-induced obesity caused impaired glucose homeostasis, distorted hepatic histoarchitecture, selected deviations in hepatic function indices, pro-inflammatory, pro-oxidant, and dsylipidaemic effects. There were evidence of escalated and reversed pathological actions following the replacement of HFD with normal diet. VCO showed no effect on glucose, insulin, insulin resistance, total protein, uric acid and TAC; but equitable effects on CAT, IL-6, CRP, ALT, AST & GGT, irrespective of the dose. Compared to the effects of VCO at 400 and 600 mg/kg, at 200 mg/kg, VCO had more significant therapeutic effects on LDH, MDA, SOD, GPX, TC, TG, LDL-C, total bilirubin, atherogenic and lee indices and hepatic histoarchitecture. Conclusively, VCO, preferably at a low dose could be used to reverse hepatic structural alteration and some biochemical deviations following dietary modifications in obese condition.

Co-administration of omega-3 fatty acids and metformin showed more desirable effects than the single therapy on indices of bone mineralisation but not gluco-regulatory and antioxidant markers in diabetic rats.

Although metformin (Met) is the most recommended anti-diabetogenic drug in type 2 diabetic state, the drug is known to compromise bone integrity. Like metformin, omega-3 fatty acids (ω-3) have gluco-regulatory action; however, it aids bone health. Therefore, the present study investigated the effects of ω-3 and/or metformin in diabetic rats. Fifty rats of ten animals per group were divided into the following: Control; Diabetic untreated; Diabetic + ω-3; Diabetic + metformin (metfm) and Diabetic + ω-3 + metf groups. Diabetes was induced by the administration of streptozotocin (65 mg/kg b.w., i.p.), 15 min after the administration of nicotinamide (110 mg/kg b.w., i.p.). Five days afterwards, treatments started and they lasted for 28 days. ω-3 and metformin were administered at 200 and 180 mg/kg b.w., p.o. respectively. The results showed that the induced diabetes was characterised by significant increases in calcium to phosphorus ratio, tartrate resistant acid phosphatase (TRAP), glucose and insulin resistance; but significant decreases in parathyroid hormone(PTH), phosphorus, TAC and hepatic glycogen. Relative to the diabetic control, treatments with ω-3 or metformin caused significant elevations in hepatic glycogen, total alkaline phosphatase (TALP), osteocalcin, PTH, estradiol, and calcium; however, significant decreases in TRAP and glucose. Co-administration of ω-3 and metformin caused more desirable effects on TALP, c-terminal telopeptide of type 1 collagen, estradiol and calcium to phosphorus ratio compared to the single administration. Relative to ω-3, melatonin showed a more favourable effect on calcium to phosphorus ratio; however, the former proved to have more desirable actions on insulin and TAC. Hence, it was concluded that the combined but not the single administration of ω-3 and metformin could be preferably used in the management of bone health in diabetic state.

Diclofenac - induced hepatotoxicity: Low dose of omega-3 fatty acids have more protective effects.

The global embrace of the Western dietary style has necessitated the need for supplementation with omega-3 fatty acids (N-3) to redress the imbalance in omega-6/omega-3 fatty acids ratio. Therefore, the study investigated the effects of pre-treatment with N-3 in adult male Wistar rats exposed to diclofenac sodium (DF). Twenty adult male Wistar rats were used for this study. They were divided into 4 groups of 5 rats each, which included: Group 1 - Normal control; Group 2 - DF control; Group 3 - Low N-3 + DF; and, Group 4 - High N-3 + DF. The rats in group 2 were administered DF (10 mg/kg b.w./day, im) during the last 7 days of the experiment, while the rats in groups 3 and 4 were pre-treated with N-3 at 100 and 300 mg/kg b.w./day, po respectively for 21 days, afterwards, they received DF at 10 mg/kg b.w./day (im) for 7 days. The result showed that DF significantly increased malondialdehyde, lactate dehydrogenase, and pro-inflammatory markers (total white blood cell count, uric acid, platelet/lymphocyte and neutrophil/lymphocyte ratios). Moreover, DF significantly elevated the activities of alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase, but, significant reduced the total antioxidant capacity and the activities of superoxide dismutase, catalase, and glutathione peroxidase. The histological results were parallel to the biochemical and haematological findings. Pre-treatment with N-3 significantly prevented the manifestation of the abnormalities brought about by DF. Although there were indications of the dose-dependent effects of N-3, the low dose was found to be more effective. In conclusion, the pre-administration of N-3, preferably at a low dose, could reduce hepatotoxicity that could result from subsequent exposure to DF.

Melatonin prevents and ameliorates lead-induced gonadotoxicity through antioxidative and hormonal mechanisms.

We investigated the effects of melatonin on sperm parameters and some biochemical markers in lead-exposed male Wistar rats. Lead (50 mg/kg bw/day) and/or melatonin (4 mg/kg or 10 mg/kg bw/day) was administered for 4 weeks, while 2-week lead exposure was preceded by or followed by 2-week treatment with both doses of melatonin in other groups. Lead reduced glutathione, catalase, adjusted testes weight, semen parameters but did not change malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase, and total antioxidant capacity. Though independent of prolactin, lead-induced gonadotoxicity was both centrally and peripherally mediated, as it reduced gonadotropin-releasing hormone and testosterone levels, while gonadotropin levels did not change significantly probably due to negative feedback by elevated estradiol. However, pre-, simultaneous, or posttreatment of lead-exposed rats with melatonin reduced MDA, SOD, and estradiol but dose-dependently increased other parameters. Conclusively, lead causes male gonadotoxicity through oxidative stress and endocrine mechanisms, and these could be dose-dependently prevented and ameliorated by melatonin.

Synergistic and non-synergistic effects of salmon calcitonin and omega - 3 fatty acids on antioxidant, anti-inflammatory, and haematological indices in diabetic rats.

The optimum therapy for the management of diabetes mellitus (DM) has been a controversial issue. Therefore, the study investigated the effects of salmon calcitonin (Sct) and/or omega-3 fatty acids {eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA); EPA/DHA ratio?=?3/2} relative to metformin in diabetic male Wistar rats. Forty rats were used for this study. They were randomly divided into 8 groups of five (5) rats each, which were treated with single or combined administration of salmon calcitonin, N-3 and metformin. DM was induced by the administration of streptozotocin (65?mg/kg b.w., i.p.), 15?min after the administration of nicotinamide (110?mg/kg b.w., i.p.). Nine days afterwards, treatments started, and they lasted for 28 days. Sct was administered at 2.5 and 5.0 IU/kg b.w./day (i.m.), while, N-3 and metformin were administered at 200 and 180?mg/kg b.w./day (p.o.) respectively. The results showed that the induced DM significantly increased pro-inflammatory markers, and significantly altered antioxidant and haematological indices. The combined administration of Sct and N-3 had synergistic effects on total bilirubin and total antioxidant capacity, but, non-synergistic actions on malondialdehyde, uric acid, interleukin-6, lactate dehydrogenase, superoxide dismutase, catalase, glutathione peroxidase, and the haematological parameters. These effects were comparable to that of metformin which showed a more or less therapeutic action than N-3. The study concluded that the antioxidant, anti-inflammatory, and haematological effects of the combined administration of Sct and N-3 is comparable to that of metformin. Nevertheless, the latter showed more or less therapeutic effects relative to N-3.

Diabetes escalates knee osteoarthritis in rats: Evidence of adaptive mechanism.

Clinical reports on the coexistence of diabetes mellitus (DM) and osteoarthritis (OA) dated back to the 1960 s. Therefore, the study investigated the effects of induced DM and/or knee osteoarthritis (KOA) on known biomarkers in male Wistar rats. Twenty rats of five animals per group were induced with DM and/or knee OA using streptozotocin plus nicotinamide and sodium monoiodoacetate. Afterwards, they were left untreated for four weeks.The results showed that pro-inflammatory and pro-oxidative events were most significantly expressed in D + OA group and least in OA group. In contrast to the other experimental groups, there was a decreased bone formation in DM group.Unexpectedly, there were significant increases in bone and cartilage degradation markers in diabetic group, relative to D + OA group. In conclusion, diabetic-osteoarthritic state is characterised by more altered biochemical profile, relative to what is probable in either disease condition. Nevertheless, this situation remains subject to the influence of endogenous homeostatic mechanisms.

Combined but not single administration of vitamin C and l-carnitine ameliorates cisplatin-induced gastric mucosa damage in male rats.

Although cisplatin is a potent anticancer drug, it instigates oxidative and pro-inflammatory reactions that pose significant and distressing clinical symptoms. Therefore, this study investigated the effects of vitamin C and (or) l-carnitine on cisplatin-induced gastric mucosa damage in rat. The rats were allocated into 6 groups (n = 5). The control group received distilled water, while the treatment groups received cisplatin alone (CIP), or cisplatin with vitamin C, l-carnitine, or their combination. Cisplatin caused disruption of the gastric mucosa histoarchitecture and altered the mucus barrier function. Moreover, the stomach tissue of the CIP-treated group showed increased levels of oxidative stress markers (malondialdehyde and H2O2) and decreased activities of antioxidant (superoxide dismutase, glutathione peroxidase, catalase, glutathione S-transferase) and non-antioxidant (reduced glutathione) enzymes. These deleterious events were accompanied with significant increases in pro-inflammatory cytokines and inflammatory infiltration markers, myeloperoxidase and inducible nitric oxide synthase. However, the administration of both vitamin C and l-carnitine, and not either of the two showed additive effects in attenuating the adverse effects of cisplatin. The histological results agreed with the biochemical assays. The study concluded that the combined administration of vitamin C and l-carnitine, but not the single therapy, could prevent the adverse effects of cisplatin on gastric tissue.

Calcitonin and Omega-3 Fatty Acids Exhibit Antagonistic and Non-Additive Effects in Experimental Diabetes.

Because optimising therapy for the management of diabetes mellitus remains challenging, the study investigated the effects of salmon calcitonin (Sct) and/or omega-3 fatty acids (N-3 - eicosapentaenoic acid and docosahexaenoic acid-3:2), compared to metformin, on selected biochemical parameters in male Wistar rats, in an experimental model of diabetes. Forty rats were used for this study. They were divided into eight groups of five rats each, which included: Normal control; Diabetic (D) control; D + N-3; D + low dose Sct (Sct. Lw); D + high dose Sct (Sct. Hi); D + N-3 + Sct.Lw; D + N-3 + Sct.Hi; and D + metformin. Diabetes was induced in overnight fasted rats by the administration of streptozotocin (65 mg/kg b.w., i.p.), 15 min after the administration of nicotinamide (110 mg/kg b.w., i.p.). Nine days later, Sct was administered at 2.5 and 5.0 IU/kg b.w./day (i.m.), while N-3 and metformin were administered at 200 and 180 mg/kg b.w./day (p.o.) respectively, for four weeks. Sct, N-3, and metformin significantly reduced total cholesterol, LDL-C, cortisol, c-telopeptide of type 1 collagen, and collagen type 2 alpha-1. The combined administration of Sct and N-3 had more favorable effects on triglyceride and HDL-C than either monotherapy. Unlike metformin and Sct. Hi, N-3 significantly reduced alkaline phosphatase activity. Moreover, N-3 significantly suppressed the hypocalcaemic, hyperglycaemic, and insulin resistance provoking actions of Sct. Furthermore, N-3 contradicted the hepatic glycogen depletion and inhibition of nitric oxide synthesis brought about by Sct. In conclusion, N-3 demonstrated antagonistic and non-additive actions with Sct. Moreover, the effects of the combined administration of Sct and N-3 were comparable to that of metformin; therefore, they might be considered as therapeutic alternatives in diabetes.

The Garcinia kola biflavonoid kolaviron attenuates experimental hepatotoxicity induced by diclofenac.

This study sought to investigate the effects of kolaviron on diclofenac-induced hepatotoxicity in rats. Sixty male Wistar rats were divided into 6 groups of 10 rats each as follows: a control group that received oral propylene glycol and treatment groups that received diclofenac alone, diclofenac followed by Livolin Forte (a reference drug), or diclofenac followed by kolaviron at three different doses. At the end of the study period, five rats per group were sacrificed under ketamine hydrochloride anesthetic, 24h after treatment, while the other 5 rats in the group were allowed to recover for 2 weeks before being sacrificed. Liver enzyme activities, total bilirubin levels, and the concentrations of several pro-inflammatory cytokines were determined using plasma samples, while liver tissue samples were used for antioxidant analysis and histopathological examination. Compared with the control group, plasma liver enzyme activities, along with bilirubin levels, were higher in the groups that received diclofenac alone or diclofenac+the highest dose of kolaviron, respectively. These groups had higher plasma concentrations of pro-inflammatory cytokines than did the control group. However, the administration of Livolin Forte and kolaviron (at the lower doses) ameliorated diclofenac-induced hepatic injury by improving antioxidant status, preventing an increase in inflammatory mediators, decreasing malondialdehyde, and attenuating the adverse effect of diclofenac on hepatic tissues. In addition, there was a significant difference in the histological scores between the groups that received either diclofenac alone or diclofenac followed by the highest dose of kolaviron when compared with the other three groups (Livolin Forte or lower doses of kolaviron). In conclusion, kolaviron appears to be as effective as Livolin in attenuating DCLF-induced hepatotoxicity in rats. However, high doses of kolaviron seem to cause damage to the liver.