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Summary: Background: Testosterone insufficiency affects bone and lipid metabolism and has been linked with metabolic syndrome. Contrarily, omega-3 fatty acids (ω-3FAs) are widely acclaimed for their favourable effects on osseous tissue and lipid homeostasis. Therefore, we investigated the dose-graded effects of ω-3FAs on indices of bone and lipid metabolism in orchidectomised rats. Methods: Fifty rats were randomised into 5 groups, viz; Control; Orchidectomised (Orchid); Orchid + Low dose ω-3FAs (Orchid + LD ω-3FAs); Orchid + Medium dose ω-3FAs (Orchid + MD ω-3FAs); and Orchid + High dose ω-3FAs (Orchid + HD ω-3FAs). ω-3FAs were administered at a low, medium and high dose of 100, 300 & 500 mg/kg BW, p.o./day respectively throughout the 10 weeks duration of the experiment. However, the control and orchid groups were administered saline (vehicle) at 1 ml/kg BW, p.o./day. Results: Relative to the control group, there was significant impairment of lipid and bone metabolism in the untreated orchid group. LD ω-3FAs had superior effects on osteocalcin and calcium, while MD ω-3FAs showed more prominent action on hydroxyproline; but, HD ω-3FAs proved to be better. The dominant effects of HD ω-3FAs were indicated by its significant action on triglyceride, very low, low and high density lipoprotein cholesterol, oestradiol and low density lipoprotein cholesterol/high density lipoprotein cholesterol ratio. Nevertheless, the effects of ω-3FAs on parathormone, phosphorus, testosterone, tartrate resistance acid phosphatase, free fatty acids, phospholipids and total cholesterol were not dose-dependent. Conclusion: HD ω-3FAs have the most desirable effects on lipid and bone metabolism in orchidectomised state.

OBJECTIVE: This study investigated the effect of bisphenol F (BPF) on testicular integrity and function. The roles of xanthine oxidase/uric acid signalling and steroidogenic enzymes were also probed. METHODOLOGY: Male Wistar rats were randomized into vehicle-treated control, BPF-treated (10, 30, and 50mg/kg), and BPF-treated recovery (animals treated with varying BPF doses and allowed a 28-day exposure free period for recovery) (n= 6 rats per group). The administration was via gavage and lasted for 28 days. Animals in the recovery groups were allowed a 28-day exposure-free period after the initial 28 days of BPF exposure.RESULTS: BPF resulted in the distortion of the testicular histoarchitecture, accompanied by a significant rise in testicular GGT and LDH activities but a decline in SDH activity. Also, BPF caused a significant reduction in plasma GnRH, LH, FSH, and testosterone, which was associated with the downregulation of testicular 3beta-hydroxysteroid dehydrogenase (3β-HSD) and 17beta-hydroxysteroid dehydrogenase(17β-HSD) activities. Furthermore, BPF induced testicular inflammation, redox imbalance, and apoptosis, accompanied by elevated xanthine oxidase activity and uric acid concentration. Again, the observed toxic effects of BPF were dose-dependent and not reversed by BPF exposure withdrawal.CONCLUSION: Bisphenol F-induced gonadotoxicity by down-regulating the activities of steroidogenic enzymes and upregulation of xanthine oxidase/uric acid signalling.

Dietary supplementation with omega-3 fatty acids have been advocated because of the global preference for the omega-6 fatty acids - rich Western style diet. The study investigated the effects of omega-3 fatty acids (combination of N-3: eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA); EPA/DHA ratio = 3/2) compared to livolin (Phosphatidylcholin + vitamins) on biochemical and haematological parameters in diclofenac (DF) - induced hepatotoxicity in male Wistar rats. Twenty five rats were used. They were divided into 5 groups (n = 5) which included: Group 1-Control (untreated); Group 2-DF control; Group 3-DF + Low N-3; Group 4-DF+High N-3; and, Group 5-DF + Livolin. Group 2 received DF at 10 mg/kg b.w. (i.m.) during the first 7days of the experiment, thereafter; they were administered distilled water (0.1 ml) for three weeks. Groups 3, 4, and 5 were pre-treated with DF during the first 7days of the experiment, afterwards, they were post-treated with N-3 and livolin at 100, 300, and 5.2 mg/kg b.w. (p.o.) respectively for 21days.The results showed that DF caused significant increases in MDA, LDH, proinflammatory markers, ALT, AST, and ALP activities, but, significant decreases in antioxidant indices. However, post-treatment with N-3 or livolin corrected these deviations. Although there was evidence of the dose dependent effects of N-3, the high dose was not always the most effective. The histological results proved that livolin has a more hepatoprotective action than N-3, although the biochemical and haematological findings attested that both therapies have comparable effects. It was concluded that livolin proffers a more protective effect than N-3 in DF-induced hepatotoxicity.

WHO encourages the addition of herbal medicine in national health care programs. Modern medicine can never be completely divorced from traditional medicine. Reactive species are produced during the metabolism of most drugs. Although aspirin is an analgesic drug, it instigates oxidative stress. Plants with antioxidant properties could be used to abate the oxidative effects of modern medicine. The extract of Vernonia amygdalina has potent antioxidant properties.

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.

BackgroundKetoconazole (Keto), an antifungal drug and a common therapeutic option in the treatment of advanced prostate cancer, is known to cause reproductive dysfunctions. Like Keto, melatonin has antifungal and anticarcinogenic actions. Moreover, the hormone has been used to reverse the damaging effects of different toxicants on the reproductive system. Therefore, this study investigated the effects of Keto with/without melatonin on selected biomarkers in rats.MethodsForty rats of 10 animals per group were used in this study, which lasted for 6 weeks. The control group was administered with saline (0.1 mL/day), while group 2 was administered with Keto during the last 3 weeks of experiment; however, in groups 3 and 4, Keto was administered during the first 3 weeks; thereafter, they were administered with saline and melatonin, respectively, during the subsequent 3 weeks. Keto and melatonin were administered at 100 and 10 mg/kg b.w./day (p.o.), respectively.ResultsThe central effects of Keto are independent of the follicle stimulating hormone (FSH) and prolactin; however, relative to the control group, the drug significantly decreased the gonadotrophin releasing hormone (GNRH) and the luteinizing hormone (LH), substantiated by the corresponding significant decreases in sperm count and sperm morphology. Keto caused significant elevations in malondialdehyde (MDA) and lactate dehydrogenase (LDH) and a significant decrease in catalase (CAT) compared with the control group. Moreover, the drug triggered pro-inflammatory events. In group 3 (Keto recovery), MDA and uric acid levels were returned to the baseline (i.e. control), but not GNRH, LH, C-reactive protein (CRP), LDH, and CAT. Treatment with melatonin after Keto administration caused significant increases in FSH, LH, superoxide dismutase, total antioxidant capacity (TAC), sperm count, and sperm morphology but significant decreases in MDA and CRP, relative to groups 2 and 3.ConclusionsMelatonin ameliorates some biochemical alterations following ketoconazole administration.

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.

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.

Graphical abstract A schematic diagram showing the protective effects of omega-3 fatty acids in diclofenac sodium − induced hepatotoxicity., Highlights • Diclofenac sodium instigates pro-oxidative and pro-inflammatory responses. • Dietary supplementation with omega-3 fatty acids (N-3) boost the antioxidant system. • Low dose of N-3 has more hepatoprotective effects than the high., 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.

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.

Highlights • The toxic effects of diclofenac (DF) seemed to be sustained after withdrawal. • DF appeared to be more toxic post-administration. • Melatonin could attenuate the toxic effects of DF., Although there are several reports on the toxic actions of sodium diclofenac (DF), there is dearth information on its effect on the male reproductive system. Therefore, the study investigated the effects of DF and melatonin in male rats. Twenty rats were used in this study, which lasted for 6 weeks. The control group (vehicle treated) received normal saline (0.1 ml/day, p.o.). In the experimental groups, DF was administered during the first (group 2) and last (group 3) three weeks of the study. However, in group 4, melatonin was administered for 3 weeks, after 3 weeks of treatment with DF. DF and melatonin were administered at 1 and 10 mg/kg b.w./day (p.o.) respectively. The results showed that unlike melatonin, DF had no effect on gonadotrophins; however, it caused significant decreases in GNRH and testosterone, but a significant increase in prolactin. Melatonin attenuated the pro-antioxidant and pro-inflammatory effects of DF, which caused significant decreases in SOD, TAC, CAT, but significant elevations in LDH, MDA, uric acid and CRP. Moreover, the hormone reversed the adverse effect of DF on sperm count, sperm motility and sperm morphology. There were slight evidence of the precipitation of imbalance in lipid metabolism by DF and the antidyslipidaemic action of melatonin. Compared to DF, DF recovery showed more adverse effects on prolactin, testosterone, LDH, MDA, UA, CRP, semen parameters (except sperm motility), TC, LDL-c, HDL-c and phospholipid. The histological results agreed with the biochemical assays. In conclusion, the reproductive toxicity effects of DF seem to escalate after withdrawal; however, these effects could be attenuated by treatment with melatonin.

In this study, we compared the anti-obesitogenic effects of virgin coconut oil (VCO), omega3 fatty acids (N-3), and orlistat in obese Wistar rats fed with normo- or hyper-lipidaemic diets. The eighty rats (n = 10) that were used for this study were divided into 8 groups. The results revealed that VCO, N-3, and orlistat showed comparable effects on lactate dehydrogenase, superoxide dismutase, c-reactive protein, gamma-glutamyltranspeptidase, alkaline phosphatase, aspartate aminotransferase, uric acid, total protein, atherogenic and Lee indices, lipid profile, and insulin resistance. However, VCO demonstrated superior actions than N-3 and orlistat on malondialdehyde, glutathione peroxidase, and interleukin -6, while orlistat and N-3 proved to have a better effect on total antioxidant capacity and alanine aminotransferase respectively. Moreover, VCO and orlistat had an equivalent but more desirable effects than N-3 on glucose and insulin resistance, while VCO and N-3 precipitated a parallel but dominant action than orlistat on total bilirubin. The histological findings largely agreed with the biochemical assays. Conclusively, like orlistat, VCO and N-3 showed considerable anti-obesitogenic effects.

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.

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.

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.

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.

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.

Clinical evidences on the coexistence of diabetes mellitus (DM) and osteoarthritis (OA) dated back to the 1960s. Therefore, the study investigated the effects of induced DM and/or knee osteoarthritis (KOA) on some biochemical and haematological parameters in adult male Wistar rats. Twenty rats were used for this study. They were randomly divided into 4 groups (N=5 rats) which included: Normal control; Osteoarthritic (OA) control; Diabetic control; and, Diabetic+Osteoarthritic (D+OA) control. DM was induced in overnight fasted rats by the administration of streptozotocin (65mg/kg b.w., i.p.) 15min after the administration of nicotinamide (110mg/kg, b.w., i.p.). However, KOA was induced by the intra-articular injection of 4mg of sodium monoiodoacetate in 40μl of normal saline. In the D+OA group, KOA was induced about 12h after the induction of DM. The rats were left untreated for four weeks. Afterwards, the experiment was terminated. The results showed that both DM and OA featured hypercortisolism and dyslipidaemia. The additive effects of both conditions were observed on the lipid profile and some haematological indices in the D+OA group. Unlike DM, OA had mild adverse effects on the haematological profile. Nevertheless, it significantly contributed to hyperglycaemia in the D+OA group, even though it had no significant effect on the insulin resistance. However, the hypocalcaemic and glycogenolytic effects of DM were negated by OA. In conclusion, the coexistence of DM and OA presents a greater challenge on the biochemical and haematological profiles than the individual disease. But, this prediction could sometimes be annulled by the intervention of endogenous homeostatic mechanisms.

Background:There is a continuous search for a better therapy in osteoarthritis (OA) management. Therefore, this study investigated the effects of salmon calcitonin (Sct) and/or omega-3 fatty acids (N-3) relative to diclofenac sodium (DF) in induced knee osteoarthritic male Wistar rats.Methods:The 40 rats that were used in this study were divided into 8 groups (n=5 rats), viz: Normal control; OA control; OA+N-3; OA+Low dose of Sct (Sct.Lw); OA+High dose of Sct (Sct.Hi); OA+N-3+SCt.Lw; OA+N-3+Sct.Hi; and, OA+DF. OA was induced with 4 mg of sodium monoiodoacetate in 40 μL of saline. The solution was injected into the left knee joint space of anaesthetised rats. Sct was administered at 2.5 and 5.0 IU/kg b.w. (Results:Sct and/or N-3 significantly reduced c-telopeptide of type 1 collagen (CTX-1), collagen type 2 α-1 (C2M), malondialdehyde (MDA), uric acid (UA), and interleukin-6 (IL-6), but, significantly increased superoxide dismutase (SOD) after OA induction. Both therapies had additive effects on C2M, MDA, SOD, and catalase (CAT), but, non-additive actions on UA, IL-6, and CTX-1. Like the Sct and N-3, DF significantly reduced CTX-1, C2M, UA, and IL-6. However, it had no significant effect on SOD and MDA, even though it significantly reduced CAT activity. None of the therapies had significant effect on total alkaline phosphatase activity, except N-3+Sct.Lw.Conclusions:The combined, and sometimes the single administration of Sct and N-3 proved to be better therapies in OA management than DF.

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.

Reports on the coexistence of diabetes mellitus and osteoarthritis in human subjects dated back to the 1960s. However, there is no account in literature on the co-manifestation of these disease conditions in experimental animals. In our previous study, we reported for the first time, the effects of pharmacological agents on glucoregulatory indices, lipid profile, and inflammatory markers in experimental diabetic-knee osteoarthritic rat. However, in the present study, the effects of salmon calcitonin (Sct), and/or omega-3 fatty acids (N-3) were further investigated on other biomarkers. Forty-nine rats of seven animals per group were used for this study. Diabetes was induced by the administration of streptozotocin (65 mg/kg) and nicotinamide (110 mg/kg). Thereafter, knee osteoarthritis was induced by the intra-articular injection of 4 mg of sodium monoiodoacetate in 40 μl of saline. Nine days after the inductions, treatments started, and they lasted for 4 weeks. N-3 was administered at 200 mg/kg/day, while Sct was administered at 2.5 and 5.0 IU/kg/day. The results of the study indicated that the induced diabetes-knee osteoarthritis caused significant alterations in all the observed biomarkers. Sct showed a dose-specific effect and an additive action with N-3 in reducing malondialdehyde and lactate dehydrogenase, and in elevating total bilirubin and total antioxidant capacity. However, it largely demonstrated a nondose-specific effect and nonadditive action with N-3 on superoxide dismutase, catalase, glutathione peroxidase, total alkaline phosphatase, c-telopeptide of type-I collagen, collagen type-2 alpha 1, and hematological indices. In conclusion, the combined administration of Sct and N-3 proffer better therapeutic effects than the single therapy; therefore, they could be used in the management of diabetic-osteoarthritic condition.