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

Ginkgo biloba extract [EGb761] normalizes hypertension in 2K, 1C hypertensive rats: roles of antioxidant mechanisms, ACE inhibiting activity and improvement of endothelial dysfunction

In the 2 kidney, 1-clip [2K, 1C] experimental renovascular hypertension, the early phase of elevation of blood pressure is associated with increase in plasma renin activity, and circulating angiotensin II which exerts a vasoconstrictor effect and increases aldosterone production. However, the progression and maintenance of the elevated blood pressure is mediated, in part, by angiotensin II-induced production of reactive oxygen species [ROS] which may promote endothelial dysfunction. The aim of the present study was to examine the possible antihypertensive effect of a standardized extract of Gingko biloba [EGb 761] in 2K,1C renal hypertensive rats and try to correlate it with the effect of the extract on oxidant status, ACE activity and vascular reactivity towards several vasoactive agents. Hypertension was induced using silver clip on renal artery by surgery. Four weeks after surgery, two sets of experiments were preformed. In the first set five groups of rats were selected; Sham-operated control, hypertensive control, and three hypertensive groups treated with the EGb 761 extract at 3 dose levels [60, 90, and 180 mg/kg/day; po] respectively for three weeks. Systolic blood pressure [SBP], heart rate [HR], lipid peroxidation measured as malondialdehyde [MDA], gIutathione peroxidase [GSH-Px] activity, nitric oxide [NO] level and angiotensin converting enzyme [ACE] activity were determined in blood, the ischemic kidney and the non-clipped contra-lateral kidney homogenates. In the second set of experiments three groups of animals were selected; Sham-operated control, hypertensive control, and hypertensive group treated with the EGb 761 [180 mg/kg/day; po] for three week after which the animals were sacrificed, the thoracic aortae isolated and prepared as rings for testing their reactivity towards the vasoactive agents norepinephrine [NE], acetyicholine [Ach], and sodium nitroprusside [SNP]. Results showed that clipping of the renal artery significantly elevated the SBP which reaches a plateau after 4 weeks, without any significant change in the HR. MDA significantly increased in serum and the clipped kidney. GSH-Px significantly decreased in the ischemic kidney while it was significantly elevated in serum and the contra-lateral kidney. NO level as well as ACE activity significantly increased in both kidneys without being affected in blood. There was impairment in both endothelium-dependent and independent relaxation of aortic rings towards Ach and SNP respectively. Treatment with EGb for 3 weeks produced a dose-dependent reduction in the SBP of the hypertensive rats and succeeded to normalize it with the highest dose level [180 mg/kg/day]. This antihypertensive action was associated with recovery of GSHPx activity in the ischemic kidney, inhibition of ACE activity in both kidneys, reduction of elevated NO in the non-clipped kidney, decreased responsiveness to the vasoconstrictor NE and improvement of endothelial function as evidenced by restoration of endothelium-dependent vasorelaxation induced by Ach

Study of the antihypertensive effect of olea europea extract [EFLA 943] in renal hypertensive rats: roles of ACE activity, redox state, and vascular liorepinephrine responsiveness

Standardized extract from leaves of Olea europea [EFLA 943] constitutes a mixture of biologically active natural products with a broad range of pharmacological activities. It has received a great deal of attention recently with respect to its cardiovascular effects. The present work has been undertaken to assess the possible potential antihypertensive effect of the extract and try to correlate it with its effect on oxidant status, ACE activity and vascular reactivity in the 2-kidney, 1-clip [2K, 1C] renal hypertensive rats. Two sets of experiments were performed. In the first set 3 groups of rats were selected; Sham-operated control, hypertensive control, and EFLA 943-trcated hypertensive groups. Hypertension was induced using silver clip on the renal artery by surgery. Four weeks after surgery, a single daily dose of 180 mg/kg/day; po of EFLA 943 was given for three weeks. Blood pressure was measured by the tail-cuff method weekly. ACE activity, malondialdehyde [MDA], glutathione peroxidase [GSHPx], total protein thiols [Pr-SHs], and nitric oxide [NO] were determined in the clipped kidney non-clipped kidney and blood. A second set of experiments with 3 groups and similar treatment like the first one was conducted but at the end of the treatment period rats were sacrificed, the thoracic aortae isolated and prepared as rings for testing their reactivity towards norepinephrine [NE], acetylcholine [Ach], and sodium nitroprusside [SNP]. Results showed that clipping of the renal artery significantly elevated the systolic blood pressure [SBP] which reaches a plateau after 4 weeks. MDA significantly increased in serum and the clipped kidney GSH-Px significantly decreased in the ischemic kidney while it was significantly elevated in serum and the contra-lateral kidney. NO level as well as ACE activity significantly increased in both kidneys without being affected in blood. There was impairment in both endothelium-dependent and independent relaxation of aortic rings towards Ach and SNP respectively. Treatment with EFLA 943 produced a significant reduction in the SBP of the hypertensive rats. This antihypertensive action was associated with inhibition of ACE activity in the non-clipped kidney, reduction of serum MDA, decrease in total Pr-SHs normalization of NO in both kidneys, and recovery of GSHPx activity in the ischemic kidney, together with decreased responsiveness to the vasoconstrictor NE

Protective effect of L-carnitine against carbon tetrachloride-induced liver injury in rats

Oxidative damage is involved in the pathogenesis of various, hepatic injuries. In the present study the capacity of L-carnitine as an antioxidant to protect against carbon tetrachloride [CCl[4]]-induced oxidative stress and hepatotoxicity in rats was Cairo. Egypt investigated. Daily oral administration of CCl[4]100 mg/kg in corn oil for 4 weeks produced a marked significant elevation in serum, alanine aminotransferase [ALT], aspartate aminotransferase [AST], alkaline phosphatase [ALP], lactate dehydrogenase [LDH], and alpha fetoprotein [AFP]. Hepatic lipid peroxidation, quantified as malondialdehyde [MDA] was significantly increased, while the activity of the two antioxidant enzymes; glutathione peroxidase [GPx] and superoxide dismutase [SOD] in the liver were significantly reduced. Histopathological and histochemical analyses of the liver of rats treated with CCl[4] revealed centrilobular necrosis with lymphocytic infiltration between hepatocytes. The hepatocytes were damaged in the form of fatty degeneration, vacuolization, ballooning with bundles of fibrous tissue surrounding the portal tracts and dissecting the parenchyma. Concurrent administration of L-carnitine [50 mg/kg/day; s.c.] with CC!4 for 4 weeks produced a significant reduction of aminotransferases together with normalization of ALP and LDH activities as well as AFP level. The biochemical parameters of oxidative stress were improved. Hepatic MDA concentration was significantly reduced, while the activities of the hepatic antioxidant enzymes GPx and SOD were significantly increased. These effects were paralleled with an improvement of the histopathological changes induced by CCl[4], where the hepatic architecture was preserved by L-carnitine treatment. Therefore, the results of this study show that L-carnitine can be proposed to protect the liver against CCl[4]-induced oxidative damage in rats, and the hepatoprotective effect might be correlated with its antioxidant and free radical scavenger effects