Montelukast, a leukotriene receptor antagonist abrogates lipopolysaccharide-induced toxicity and oxidative stress in rat liver.

Endotoxemia-induced hepatotoxicity is characterized by disturbed intracellular redox balance, excessive reactive oxygen species (ROS) generation inducing DNA, proteins and membrane lipid damages. In the present study, the protective effects of montelukast (MNT) against Escherichia coli lipopolysaccharides (LPS)-induced oxidative stress were investigated in rat liver. LPS (10mg/kg, i.p.) was injected and the animals were sacrificed 6h after LPS challenge. MNT (10mg/kg) was administered orally for seven successive days before endotoxemia induction. Blood samples were withdrawn for assessing the activities of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), lactate dehydrogenase (LDH) and levels of serum total bilirubin, total protein, tumor necrosis factor-alpha (TNF-α) and interleukin 1ß (IL-1ß). Livers were dissected out and used for histological examination or stored for the determination of malondialdehyde (MDA), protein carbonyl content (PCC), reduced glutathione (GSH) levels, enzymatic activities of catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and myeloperoxidase (MPO). Sepsis significantly increased ALT, AST, ALP, LDH, total bilirubin, TNF-α and IL-1ß, MPO, MDA and PCC levels and decreased total protein, GSH and enzymatic antioxidants (CAT, SOD and GSH-Px). MNT decreased the markers of liver injury (AST, ALT, ALP, LDH, and total bilirubin), inflammatory biomarkers (TNF-alpha, IL-1ß), MDA, PCC and MPO after LPS challenge. In conclusion, MNT abrogates LPS-induced markers of liver injury and suppresses the release of inflammatory and oxidative stress markers via its antioxidant properties and enhancement enzymatic antioxidant activities.

Modulating effect of ginger extract on rats with ulcerative colitis.

ETHNOPHARMACOLOGICAL RELEVANCE: Ginger rhizomes are used traditionally for management of different gastrointestinal disturbances. Several studies proved that the rhizome possesses diverse biological activities such as cytotoxic, antioxidant, and anti-inflammatory effects. Recently, interest in ginger for treatment of chronic inflammatory conditions has been renewed. AIM OF THE STUDY: The purpose of the present study is to evaluate the potential role of ginger extract [GE] in modulating the extent and severity of ulcerative colitis (UC), a chronically recurrent inflammatory bowel disease of unknown origin. MATERIALS AND METHODS: Male Wistar rats received 3 different doses of GE, sulfasalazine, or vehicle for 3 consecutive days before induction of UC by intra-rectal acetic acid administration, and continued further for 7 days after the induction. The colonic mucosal injury was assessed by macroscopic scoring, and histological examination. Furthermore, the mucosal content of malondialdehyde (MDA), protein carbonyl (PCO), and reduced glutathione (GSH) with the catalase (CAT) and superoxide dismutase (SOD) activity, were appraised as parameters of the redox state. Acute inflammatory response was determined by measuring myeloperoxidase (MPO), tumor necrosis factor (TNF-alpha), and prostaglandin E2 (PGE2). RESULTS: All parameters were altered in ulcerated rats, and improved in animals receiving GE, an effect that was comparable to that of the standard sulfasalazine, especially at the highest dose level. Colonic mucosal injury parallels with the histological and biochemical evaluations. CONCLUSIONS: Results showed a valuable effect of ginger extract against acetic acid-induced ulcerative colitis possibly by its antioxidant and anti-inflammatory properties.

Can nitric oxide-generating compounds improve the oxidative stress response in experimentally diabetic rats?

1. The present study was designed to evaluate the protective effects of the nitric oxide (NO)-generating compounds L-arginine (L-Arg) and sodium nitroprusside (SNP) on oxidative stress markers in streptozotocin (STZ)-diabetic rats. 2. Diabetes was induced after a single intraperitoneal injection of STZ (60 mg/kg). Rats were divided into non-diabetic (control), diabetic and treated diabetic groups. The treated diabetic groups were supplemented with L-Arg (300 mg/kg), SNP (3 mg/kg per day) or glibenclamide (0.6 mg/kg per day) orally for 4 weeks. 3. At the end of the experiment, fasted rats were killed by cervical decapitation. Blood was collected for estimation of glucose, haemoglobin, glycosylated haemoglobin (HbA(1c)), total cholesterol, high-density lipoprotein-cholesterol and triglycerides. Thiobarbituric acid-reactive substances (TBARS; an index of lipid peroxidation), superoxide dismutase, glutathione peroxidase, catalase, nitrate/nitrite (NO(x)) and reduced glutathione (GSH) were estimated in liver and kidney homogenates. 4. A significant increase was observed in plasma glucose levels and HbA(1c), with a concomitant decrease in haemoglobin levels, in diabetic rats. These alterations reverted back to near normal after treatment with the NO-generating compounds. A loss of bodyweight, polydipsia, polyphagia and elevated levels of serum cholesterol and triglycerides were observed in diabetic rats. Hyperglycaemia was accompanied by a significant increase in tissue TBARS and a decrease in NO(x), GSH and anti-oxidant enzymes, whereas, supplementation with L-Arg and SNP significantly reduced TBARS levels and increased GSH and anti-oxidant enzyme activities. Linear regression analysis indicated that blood glucose and TBARS had a significant positive correlation with HbA(1c), whereas a negative correlation was observed between GSH and NO(x). 5. It is concluded that NO-generating compounds improve most of the biochemical abnormalities and anti-oxidant levels in diabetic rats. The beneficial effects of NO-generating compounds can be attributed to the generation of NO and/or enhanced anti-oxidant enzyme activities.