Localization of cyclooxygenase-2 in mice testis and assessment of its possible role through suppressing its expression using nimesulide: a preferential cyclooxygenase-2 inhibitor.

Present generation non-steroidal anti-inflammatory drugs (NSAID) are potent inhibitors of the enzyme cyclooxygenase-2 (COX-2). Even though they exhibit reduced incidence of gastrotoxicity, severe nephrotoxicity and other side effects have been widely reported with respect to usage of these drugs. Since COX-2 levels are not only upregulated by inflammation but also by other stimuli such as cytokines, growth factors, mitogens and steroid hormones, we investigated the localization of COX-2 and activity of both COX-1 and COX-2 in mice testis. To correlate the localization of COX-2 with its function we suppressed COX-2 expression with the aid of nimesulide a preferential COX-2 inhibitor. We found COX-2 was constitutively expressed in the Leydig cells of mice testis suggesting a role on testosterone synthesis. Suppression of COX-2 resulted in increased concentration of most of polyunsaturated fatty acids especially arachidonic acid (AA). Prostaglandin (PG) levels which showed an initial decline during nimesulide treatment had a reversible effect during prolonged treatment. These findings state that cyclooxygenase is constitutively expressed in mice testis and continuous inhibition of COX-2 interferes in maturation of sperm.

Hepatoprotective role of ferulic acid: a dose-dependent study.

Alcohol use is contributing to an unprecedented decline in life expectancy. Damage to the liver after ethanol administration is a well-known phenomenon. Free radical mechanisms have been proposed to play a part in ethanol-induced liver toxicity. Ingestion of diets rich in polyunsaturated fatty acids (PUFAs) along with alcohol is known to result in enhanced liver damage. The present work is aimed at evaluating the protective role of ferulic acid, a naturally occurring plant component, on alcohol- and PUFA-induced liver toxicity. Three different doses of ferulic acid (10, 20, and 40 mg/kg of body weight) were administered to rats given alcohol, heated PUFA (DeltaPUFA), and alcohol + DeltaPUFA. Influence of ferulic acid on alcohol-and PUFA-induced liver damage was evaluated by analyzing the activities of the liver marker enzymes alkaline phosphatase, gamma-glutamyl transferase, alanine transaminase, and aspartate transaminase. The activities of these liver marker enzymes were increased in the alcohol, DeltaPUFA, and alcohol + DeltaPUFA groups but were decreased significantly on treatment with ferulic acid. The low dose (10 mg/kg of body weight) was not effective, but both 20 mg and 40 mg/kg of body weight were found to be effective. The 20 mg/kg of body weight dose was found to be more effective than 40 mg/kg of body weight (the high dose). The administration of ferulic acid to normal rats did not produce any harmful effects. Thus our results show that ferulic acid is an effective anti-hepatotoxic agent without side effects and may be a good candidate in the current search for a natural hepatoprotective agent.