Hepatotoxicity induced by chronic suppurative otitis media in rats and effects of ceftazidime and amikacin on it.

Chronic suppurative otitis media (CSOM) is the chronic inflammation with perforation of middle ear. If CSOM is not treated, it may cause secondary inflammation of liver with elevated liver enzymes and histological changes. Present study is aimed to observe the hepatotoxic effects due chronic suppurative otitis media (CSOM) in CSOM induced rats and alsoto observe the effects of ceftazidime and amikacin to attenuate hepatotoxicity due to CSOM. Liver enzyme tests and histological examinations were performed on rats divided into different groups as G1 (negative control), G2 (positive control), G3 ceftizidime (15mg/kgintraperitonelly) and G4 amikacin (15mg/kg). One-way ANOVA showed that liver enzymes were significantly increased (p=0.000 and F value 6.899) except gamma glutamic transferase in G2 (rats with CSOM without treatment) from G1 (negative control without CSOM) with histological damage of liver. These hepatotoxic effects were attenuated or recover with proper treatment with potent antibiotics (ceftazidime and amikacin). Therefore, study showed that chronic suppurative otitis media can induce hepatic toxicity including elevated liver enzymes level and inflammation, aggregation or infiltration in liver cells in rat model with reversible hepatic damage. If CSOM is treated with adult dose of ceftazidime or amikacin, it may attenuate the damage and prevent risk of liver damage.

Inhibition of diet-restriction-induced behavioral deficits by tryptophan administration in rats.

Diet has a great impact on brain health and function. It plays an important role to improve and control a number of psychiatric disorders such as depression, anxiety, hyperactivity and behavioral impulsivity. Anorexia Nervosa (AN) is one of the psychiatric disorder which is associated with diet. In AN, patients show extreme dieting, weight loss, hyperactivity, depression/anxiety, self-control and behavioral impulsivity. Previous studies showed that during diet restriction, tryptophan decreases serotonin (5-hydroxytryptamine; 5-HT) metabolism in the brain due to its less availability and contributes psychiatric problems associated with AN. The present study is designed to investigate the effects of tryptophan administration on 5-HT metabolism in diet-restricted rats. Tryptophan at a dose of 50 or 100mg/kg was given orally to respective freely fed (FF) or diet restricted (DR) animals daily for five weeks. Behavioral activities were also monitored weekly. The results show significant effect (p<0.05) on behavior in activity box, open field and in light/dark transition test by tryptophan administration in diet-restricted rats. This may be associated with the increased in serum tryptophan and brain 5-HT metabolism. Therefore, it is concluded that diet-restriction-induced behavioral changes might be reverted back with the administration of tryptophan and may be helpful to improve psychological problems in AN.

Determination of tryptophan in raw materials, rat brain and human plasma by RP-HPLC technique.

This paper describes tryptophan (TRP) estimation in raw human plasma and rat brain by reversed-phase high-performance liquid chromatography (RP-HPLC). Estimation was carried out on a Purospher STAR C18 column using water-acetonitrile (90:10 v/v, at pH 2.7) mixture at a rate of 1.5 mL/min as mobile phase. Eluents were monitored at 273 nm by an ultraviolet detector. The method was linear (R(2) > 0.999), precise (intra-day and inter-day precision <2%) in the range of 0.25-20 µg/mL. The detection and quantification limits were 0.0144 µg/mL and 0.0437 µg/mL, respectively. In human plasma, Day 1 and Day 2 precision were 0.054-2.29% and 1.66-3.7%; whereas precisions in rat brain were 1.23-2.3% and 0.677-4.2%, respectively. The method was applied to study TRP level in human smokers and in arthritic rat brain. An efficient RP-HPLC method was developed for TRP determination that worked for clinical and research purposes.

Role of tryptophan in the pathogenesis of hepatic encephalopathy.

OBJECTIVE: To monitor serum levels of total and free tyryptophan in various hepatic dysregulations. METHOD: The study was conducted on 36 adult patients. All were suffering from acute or chronic liver diseases such as hepatitis (n = 12), cirrhosis (n = 12) and Hepatic Encephalopathy (HE) (n = 12). Patients of all age groups and both genders were included. Serum levels of Tyryptophan (TRP) were measured by HPLC-EC. Albumin and bilirubin were analyzed by kit method (Merck). RESULTS: The serum levels of total TRP (p < 0.01) was found in all patients. Free TRP significantly (p < 0.01) increased only in HE. Patients with hepatitis and cirrhosis did not show significant change in serum free TRP. The Albumin levels significantly decreased in hepatitis, cirrhosis and in HE (p < 0.01). All patients exhibited hypoalbuminaemia (p < 0.01). CONCLUSIONS: The results suggest that an increased ratio of free to bound TRP enhances its availability to the brain, which in turn increases 5-HT synthesis thus precipitating encephalopathy.