Modulation of carbon tetrachloride-induced hepatic oxidative stress, injury and fibrosis by olmesartan and omega-3.

This study was designed to investigate the potential effects of omega-3, olmesartan and their combination on established hepatic fibrosis in the carbon tetrachloride (CCl4) rat model. Male Wistar rats received subcutaneous injections of CCl4 twice weekly for 12weeks, as well as daily oral treatments of olmesartan (1 and 3mg/kg), omega-3 (75 and 150mg/kg) and their combination during the last 4weeks of intoxication. Our results indicated that omega-3 and, to a lesser extent, olmesartan dose-dependently blunted CCl4-induced necroinflammation scoring and elevation of liver injury parameters in serum. Besides, omega-3 and, to a lesser extent, olmesartan treatments in a dose dependent manner attenuated CCl4-induced liver fibrosis, as demonstrated by hepatic histopathology scoring and 4-hydroxyproline content. The mechanisms behind these beneficial effects of both omega-3 and olmesartan were also elucidated. These include (1) counteracting hepatic oxidative stress and augmenting hepatic antioxidants; (2) preventing the activation of hepatic stellate cells (HSCs), as denoted by reducing α-smooth muscle actin (α-SMA) expression in the liver; (3) inhibiting the proliferation and chemotaxis of HSCs, as evidenced by downregulating platelet-derived growth factor receptors-ß (PDGFR-ß) expression in the liver; and (4) inhibiting the fibrogenesis response of HSCs, as indicated by inhibiting the secretion of transforming growth factor-ß1 (TGF-ß1). Unexpectedly, when olmesartan was co-administered with omega-3, it interfered with the hepatoprotective and anti-fibrotic activities of omega-3. In conclusion, this study introduces the first evidence regarding the pronounced anti-fibrotic activity of omega-3 and suggests that it may be beneficial in the treatment of hepatic fibrosis in humans.

Protective potential of MMR vaccine against complete Freund's adjuvant-induced inflammation in rats.

The aim of the present study was to investigate the effect of MMR vaccine on inflammation which was induced by complete Freund's adjuvant (CFA) in male Sprague-Dawley rats. Rats were randomly divided into the control, CFA, MMR and CFA + MMR groups. Inflammatory symptoms such as paw oedema was measured in CFA-injected rats' paw. Body weight changes and alterations in some haematological parameters and oxidative stress markers following CFA injection were checked. In CFA-inflammed rats, there was a significant increase in rat paw thickness and decrease in body weight increment. MMR exhibited a significant anti-inflammatory effect as manifested by reduction in paw thickness and normal gain in body weight when administered 1 week prior to induction of inflammation. The altered haematological parameters (TLC) and oxidative stress markers (MDA, GSH, SOD) in the inflammed rats were significantly brought back to near normal by MMR treatment. In conclusion, MMR vaccine showed a reduction in rat paw thickness and it could significantly normalize the haematological and biochemical abnormalities in CFA-induced inflammatory pain model in rats. Our data suggested that MMR could be a potential protective agent against certain types of inflammatory pain. Further histopathological and radiological studies are required to confirm the possibility of developing novel therapeutic vaccines against some forms of arthritis.

Effects of L-carnitine and ginkgo biloba extract (EG b 761) in experimental bleomycin-induced lung fibrosis.

The effects of Ginkgo biloba extract (EGb 761) and L-carnitine on bleomycin (BLM)-induced lung fibrosis were studied in rats. BLM (cumulative dose of 180 mgkg(-1)) was given intraperitoneally (i.p.) three times weekly for 4 consecutive weeks. Treatment with BLM enhanced the responsiveness of isolated pulmonary arterial rings to serotonin (5-HT), significantly increased the normal serum level of tumour necrosis factor (TNF-alpha) by approximately 105% and markedly elevated the level of lipid peroxide (LPO) and collagen content in the lung homogenates by 34 and 83%, respectively. EGb 761 (100 mgkg(-1) ), given in drinking water for the whole study period, totally abolished the BLM-induced alterations in the measured biochemical and pharmacological parameters. Meanwhile, L-carnitine (500 mg kg(-1) ), administered in drinking water, significantly decreased the BLM-induced elevations of serum TNF-alpha, LPO level in lung tissues and the enhanced responsiveness of pulmonary arterial rings to 5-HT. However,L-carnitine did not reduce the increase in the collagen content produced by BLM. The results of the present study indicate the beneficial effects of EGb 761 and L-carnitine against lung toxicity induced by BLM treatment. Furthermore, the present data shows the advantageous use of EGb 761 as a protective agent in BLM-induced lung fibrosis under the experimental circumstances.