Taurine: a promising agent of therapeutic potential in experimentally-induced arthritis

Taurine is an amino acid whose protective effects were shown in certain inflammatory conditions. The present work aimed to explore the possible anti-arthritic effects of taurine in comparison with diclofenac. Rats were allocated into five groups [n = 10]. The normal and control groups received normal saline. The remaining three groups were treated with diclofenac [2 mg/kg], taurine [5 mg/kg], or taurine [50 mg/kg], respectively. Drugs were i.p. injected for 26 successive days starting from the onset of adjuvant induction. Arthritis was induced by s.c. injection of 0.4 ml of Freund's complete adjuvant [FCA] into the subplantar region of the right hind paws of rats in all groups except the normal one. Paw volume was measured before and at different time intervals after adjuvant inoculation. After the last measurement, blood samples were collected and were used for estimation of serum levels of lipid peroxides, nitrite, total antioxidants, tumor necrosis factor-alpha, and interleukin-1beta as well as lactate dehydrogenase activity. Histopathological examination of knee tissues of all rats was also performed. Injection of FCA induced marked arthritis manifested by paw edema during the 26-day experiment period. Treatment with diclofenac or taurine [50 mg/kg] markedly inhibited adjuvant arthritis as well as its associated biochemical and histological changes. Taurine [5 mg/kg] did not affect FCA-induced paw edema but it attenuated some of the induced biochemical changes. Taurine effects could be explained by inhibition of pro-inflammatory cytokines production as well as its antioxidant effects

New Zealand green-lipped mussel Verna canaliculus possesses an anti-inflammatory activity in the rat adjuvant arthritis with no ulcerogenic effect: the role of cytokines and antioxidant mechanisms

This study investigated the possible prophylactic and therapeutic anti-inflammatory effect of New Zealand green-lipped mussel [NZGLM] in adjuvant arthritis [AA] as well as its probable ulcerogenic activity in comparison with other NSAIDs used in arthritic disorders and the likely mechanisms underlying these potential effects. Arthritis was induced by s.c. injection of Freund's complete adjuvant into the right hind paw of Wistar rats of all groups except the normal one. The adjuvant was injected in one of the footpads to allow study of the acute inflammatory reaction in that local area of the injected paw as well as the immunological reaction that develops approximately 9 days later in the contralateral paw. Treatments with diclofenac [2 mg/kg/po] and NZGLM [250, 1000 mg/kg/po] were initiated on day 0, which is the day of adjuvant injection [prophylactic model dosing] or day 9 [therapeutic model] and continued once daily till day 21. The normal group and a control arthritic group were given oral 1% Tween 80. Both the injected and the contralateral paws' volumes were measured before adjuvant inoculation and then every 2-3 days by volume displacement. After the last measurement, blood samples were collected and were used for serum determination of tumor necrosis factor-a [TNF-alpha], interleukin-1 p [IL-1[3], malondialdehyde and nitrite. In the ulcerogenicity study, rats were injected with the adjuvant in the hind paw and at day 16 post-induction, the A A rats were then divided into 3 groups, 2 groups were treated daily for 5 days with indomethacin [3 mg/kg/po] or NZGLM [1000 mg/kg/po], while the 3rd group served as control. The animals were fasted for 20 hrs on day 4 prior to the final dose and then sacrificed 4 hrs after the, final dose of drug and their stomachs were removed, and examined for the total lesion score. Gastric mucosal homogenates were used for the estimation of lipid peroxides and myeloperoxidase activity. NZGLM exerted a significant dose-dependent anti-inflammatory effect in the AA model, its higher dose being comparable to that of diclofenac and that this effect is likely to be mediated by inhibiting the proinflammatory cytokines; TNF-alpha and IL-lp and through its antioxidant properties. In contrast to indomethacin, NZGLM did not produce any significant ulcerogenic effect

Role of pioglitazone, simvastatin and their combination in ameliorating complications of high fructose diet in rats

Recently, TNF-alpha was found to play an important role in development of insulin resistance, one of the hallmarks of metabolic syndrome. The current study aimed to investigate the effect of pioglitazone [PIO] and simvastatin [SIM] on serum level of tumor necrosis factor-alpha [TNF-alpha], as well as on the metabolic perturbations and disturbed homeostasis of glucose and lipids in a fructose-induced insulin resistance [HFD] rat model. To this end sixty male Wistar rats were divided into two dietary regimen-groups that lasted for a period of 8 weeks. Ten rats were fed normal chow and served as normal group [control]. Fifty rats were fed a fructose rich chow containing 60% fructose, 5% fat and 20% protein for a period of 8 weeks. Following confirmation of insulin resistance, rats obtained from the latter group were further subdivided into 4 groups [10 rats; each]. GpI: high fructose diet group [HFD]; Gp II: HFD + PIO [10 mg kg-1]; GpIII: HFD + SIM [20 mg kg-1]; Gp IV: HFD + a combination of PIO/SIM for two weeks. Fructose-fed rats developed insulin resistance [IR] as manifested by the significant increase in body weight, serum levels of glucose, glycosylated hemoglobin [HbA1c], insulin, homeostasis model of assessment insulin resistance index [HOMA-IR index], Triglycerides [TG], Total cholesterol [T-Chol], low density lipoprotein cholesterol [LDL-C] and significant decrease in high density lipoprotein cholesterol [HDL-C]. increase in serum TNF-alpha, as well as increased ratios of epidedymal fat/body weight, visceral fat/body weight and liver weight/ body weight were prominent findings in this study. The results revealed a positive correlation between TNF-alpha and HOMA IR-index. Treatment with PIO or SIM significantly reduced serum glucose, insulin HbA1c, TO, T-Chol, LDL-C and increase of HDL-C. A significant decrease in TNF-alpha, were observed, as well as normalization of increased percentage ratios of epidedymal fat/body weight, visceral fat/body weight and liver weight/body weight. Treatment with PIO or SIM significantly improved disturbed glucose metabolism and HOMA-IR index, co-administration of SIM and PIO synergistically enhanced the overall metabolic parameters

Effects of certain natural products in adjuvant-induced arthritis

The effects of curcumin [80 mg/kg; p.o.] and quercetin [50 mg/kg; p.o.],alone or combined, with diclofenac [2 mg/kg; i.p.] on adjuvant-induced arthritis in rats were studied and compared with diclofenac monotherapy. Experimental arthritis was induced by s.c. injection of 0.4 ml Freund's complete adjuvant [FCA] into the subplanter tissue of the right hind paw of all rats except the normal group [1% tween 80; p.o.]. The test agents were administered daily for 28 days starting from the 1[st] day of adjuvant inoculation. The control arthritic group received the vehicle [1% tween 80; p.o.] daily for the whole experiment period. Assessment of the anti-inflammatory effects of different treatments was done by measurement of paw volume before FCA injection and at different time intervals, for 28 days, thereafter using water plethysmometer. Collection of blood samples was carried out after the last paw measurement [day 28]. They were used for determination of serum lactate dehydrogenase [LDH] activity and levels of serum total antioxidants, tumor necrosis factor-alpha [TNF-alpha], interleukin-1 beta [IL-1 beta], calcium [Ca[2+]] and nitrite, a stable metabolite of nitric oxide [NO] which reflects its level. In addition, the level of thiobarbituric acid reactive substances [TBARS], as an index of lipid peroxidation was also determined. Histopathological examination of paw tissues was also carried out. Injection of FCA into the hind paw of rats induced marked arthritis manifested by paw edema during the 28-day experiment period. Treatment with diclofenac alone markedly inhibited adjuvant-induced arthritis at all the studied time intervals. Curcumin, alone, reduced FCA induced edema at day 19 only and its combination with diclofenac antagonized the anti-inflammatory effect of the latter at all the studied time intervals. Quercetin, on the other hand, reduced edema during the chronic phase of arthritis at days 19 and 28 and its combination with diclofenac antagonized the anti-inflammatory effect of the latter at day 11 only. FCA resulted in increased levels of serum TBARS, TNF-alpha, IL-1beta and nitrite as well as increased serum LDH activity. Whereas, no significant changes on serum total antioxidants or Ca[2+] levels were noted. Treatments with curcumin or quercetin alone or combined with diclofenac attenuated most of the biochemical changes elicited by FCA. Histopathological examination of paw tissues showed marked vacuolar degeneration and degradation of articular surfaces by FCA injection. Diclofenac and curcumin, alone or combined together, markedly attenuated FCA-induced histopathological changes. On the other hand, quercetin alone or in combination with diclofenac was less protective. In conclusion, the effect of diclofenac monotherapy was still superior compared to curcumin and quercetin. Effects of curcumin and quercetin seem to be mediated through influences on production of pro-inflammatory cytokines, NO level as well as lipid peroxidation

Nephrotoxicity induced by long-term administration of paraquat in rats: protective effects of quercetin and extracts of malt and green tea

Paraquat [PQ], a well-known herbicide, causes nephrotoxicity mediate by redox-cycling and extensive production of superoxide anions in the kidney. The possible protective effects of three natural products namely; green tea extract [I mg/kg], malt extract [625 mg/kg] and quercetin [50 mg/kg], against nephrotoxicity induced by long-term administration of PQ in rats were examined. PQ was intraperitoneally injected once weekly [20 mg/kg] with or without oral daily treatment with any of the three agents for 6 consecutive weeks. Nephrotoxicity was assessed by measuring serum creatinine level, histological examination of kidney sections and calculation of percentage kidney-to-body weight of rats. In addition changes in enzymatic activities of superoxide dismutase [SOD], lactate dehydrogenase [LDH] and myeloperoxidase [MPO], as well as reduced glutathione [GSH], protein thiols [Pr-SHs] and total nitrate/nitrite [NOx] contents of renal tissues were determined. Renal lipid peroxidation was also assessed by measurement of the levels of thiobarbituric acid reactive substances [TBARS]. PQ administration resulted in marked nephrotoxicity manifested by severe increase in serum creatinine level accompanied by changes in renal oxidant status of rats demonstrated by elevated TBARS level and increased activities of MPO and SOD. PQ also resulted in depletion of renal GSH and NOx contents as well as reduced activity of cytosolic LDH. On the other hand, no significant effect was noted on percentage kidney-to-body weight of rats or on renal Pr-SHs contents. Six weeks of regular daily treatment with any of the chosen agents significantly protected against most of PQ-induced biochemical changes. Histological examinations of kidney morphological changes revealed marked lesions with PQ especially in renal proximal tubules and variable degrees of protection by the test agents with the best results produced by malt extract and quercetin and to lesser extent by green tea extract. It could be concluded that malt extract and quercetin offered remarkable protection against PQ-induced nephrotoxicity in rats. Green tea extract produced some beneficial effects on the biochemical events associated with PQ-induced nephrotoxi city