Inhibitory Effects of Apium graveolens on Xanthine Oxidase Activity and Serum Uric Acid Levels in Hyperuricemic Mice.

Celery (Apium graveolens) is traditionally used to treat rheumatism and cardiovascular disorders. Hyperuricemia is considered as a predisposing factor for gout and is also suggested to be associated with coronary artery disease. In the present study, the effect of hydroalcoholic extracts from A. graveolens (AGE) against potassium oxonate (PO)-induced hyperuricemia was investigated in mice. AGE (250, 500, and 1,000 mg/kg) or allopurinol (5 mg/kg, as positive control) were orally administrated 1 h after PO injection (250 mg/kg, ip) for two weeks. After that, the serum uric acid level and hepatic xanthine dehydrogenase (XDH) and xanthine oxidase (XO) activities were measured. In addition, the antioxidant activity of AGE was determined by assessment of hepatic lipid peroxidation, in vivo and the ferric reducing/antioxidant power assay, in vitro. The extract exhibited good capacity to reduce ferric ion to ferrous ion with mean value of 63.8±8.5 µmol/g. The data also showed that oxonate treatment produced a significant increase in serum uric acid level (4.6 vs. 2.3 mg/ dL, P<0.001), liver XO/XDH activities (P<0.01 and P<0.001, respectively), and hepatic lipid peroxides levels (about two fold, P<0.01), compared to the healthy mice. AGE significantly decreased the serum uric acid level, hepatic XO/XDH activities, and lipid peroxidation, in a dose-dependent manner. Oral administration of 1,000 mg/kg AGE for two weeks reversed the elevated serum uric acid level (2.7 vs. 4.6 mg/dL, P<0.001) and significantly inhibited liver XO/XDH activities (P<0.001) and diminished hepatic lipid peroxidation (0.45 vs. 0.82 nmol/mg protein, P<0.05), compared with hyperuricemic mice. AGE (1,000 mg/kg) per se did not significantly modify these parameters. Our results demonstrated that AGE could reduce the serum uric acid level via inhibition of hepatic XDH/XO and indicated its potential utility as an effective hypouricemic bioactive agent or functional food.

PROTECTIVE EFFECT OF POMEGRANATE SEED OIL AGAINST MERCURIC CHLORIDE-INDUCED HEPATOTOXICITY IN RAT.

Mercuric chloride (HgCL2) is an environmental and industrial toxicant that affects many tissues. Considering oxidative stress is an important component of mercury induced hepatotoxicity, antioxidants are expected to play a protective role against it. The present study was designed to investigate the probable effects of pomegranate seed oil (PSO) on hepatotoxicity induced by HgCL2, administration in rats. Rats were divided into five groups. Group 1 and 2 received corn oil (1 mL/kg, i.p.) and PSO (0.8 mL/kg, i.p.), respectively. Group 3 was treated with HgCl, (5 mg/kg, i.p.) for 3 days. In groups 4 and 5 PSO (0.4 and 0.8 mL/kg i.p., respectively) was given 1 h before HgCl2 administration. Twenty four hours after last injection of HgCl2, blood samples and specimens of liver were taken. HgCl2 administration led to significant increase in liver malondialdehyde level, significant reduction in total sulfhydryl content and significant changes in serum alanine aminotransferase (ALT) and aspartate aminotransferase activity (AST), compared to control group. The histopathological changes such as necrosis, inflammatory cell infiltration and hepatocellular vacuolization were observed. PSO administration (0.8 mL/kg i.p.) improved the liver function in HgCL2 intoxicated animals as indicated by the significant decline in increased levels of AST, ALT in serum, MDA level and significant elevation in decreased total sulfhydryl content. Histological studies revealed milder hepatic lesions in PSO treated samples. The results indicated that oxidative stress may be an important mechanism of HgCl2 induced hepatic injury and dysfunction and PSO may be a useful agent for the prevention of HgCl2 induced oxidative damage in rat liver.

Protective effect of pomegranate seed oil against cisplatin-induced nephrotoxicity in rat.

PURPOSE: Clinical use of cisplatin is limited by its nephrotoxicity. Cisplatin-induced nephrotoxicity is associated with an increase in oxidative stress, leading ultimately to kidney dysfunction. The aim of this study was to investigate the effect of pomegranate seed oil against nephrotoxicity induced by cisplatin in adult rats. METHODS: Animals were divided into four groups. Group I received corn oil (1 mL/kg). Group II received cisplatin (8 mg/kg). Group III and IV received pomegranate seed oil (PSO) 0.4 mL/kg and 0.8 mL/kg one hour before cisplatin injection for 3 days, respectively. Blood samples were collected by cardiac puncture and used for measuring urea and creatinine concentration. Twenty-hour urine samples were collected to measure protein and glucose concentration. The right kidney fixed in formalin for histological examination and the left kidney was homogenized for measurement of malondialdehyde and total sulfhydryl groups. RESULTS: A significant elevation of serum creatinine, urea, urinary glucose, protein concentrations, and non-significant decrease in total thiol content and increase in MDA level in kidney homogenates were observed in cisplatin-treated rats. Also cisplatin reduced animal's body weight. Mild-to-moderate tubular cell necrosis, hyaline casts, and vascular congestion were observed in group II. PSO pre-treatment significantly decreased urinary protein, glucose, and serum creatinine concentration. PSO also caused a decrease in serum urea, renal MDA, and increase in thiol content, but the level of these parameters were not significant. CONCLUSION: The present results suggest that PSO is an effective agent for the prevention of cisplatin-induced renal dysfunction and oxidative damage in rat.

Protective effect of pomegranate seed oil against cisplatin-induced nephrotoxicity in rat.

PURPOSE: Clinical use of cisplatin is limited by its nephrotoxicity. Cisplatin-induced nephrotoxicity is associated with an increase in oxidative stress, leading ultimately to kidney dysfunction. The aim of this study was to investigate the effect of pomegranate seed oil against nephrotoxicity induced by cisplatin in adult rats. METHODS: Animals were divided into four groups. Group I received corn oil (1 mL/kg). Group II received cisplatin (8 mg/kg). Group III and IV received pomegranate seed oil (PSO) 0.4 mL/kg and 0.8 mL/kg one hour before cisplatin injection for 3 days, respectively. Blood samples were collected by cardiac puncture and used for measuring urea and creatinine concentration. Twenty-hour urine samples were collected to measure protein and glucose concentration. The right kidney fixed in formalin for histological examination and the left kidney was homogenized for measurement of malondialdehyde and total sulfhydryl groups. RESULTS: A significant elevation of serum creatinine, urea, urinary glucose, protein concentrations, and non-significant decrease in total thiol content and increase in MDA level in kidney homogenates were observed in cisplatin-treated rats. Also cisplatin reduced animal's body weight. Mild-to-moderate tubular cell necrosis, hyaline casts, and vascular congestion were observed in group II. PSO pre-treatment significantly decreased urinary protein, glucose, and serum creatinine concentration. PSO also caused a decrease in serum urea, renal MDA, and increase in thiol content, but the level of these parameters were not significant. CONCLUSION: The present results suggest that PSO is an effective agent for the prevention of cisplatin-induced renal dysfunction and oxidative damage in rat.

Protective effect of pomegranate seed oil against mercuric chloride-induced nephrotoxicity in rat.

PURPOSE: Heavy metals such as mercury can induce the generation of free radicals and oxidative stress which are associated with tissue injury. The present study was designed to evaluate the protective effect of pomegranate seed oil against HgCl2-induced nephrotoxicity. METHODS: Twenty-four W/A adult rats were randomly divided into four groups. Group I received corn oil (1 mL/kg). Group II received HgCl2 (5 mg/kg) for 3 days. Group III and IV received PSO 0.4 mL/kg and 0.8 mL/kg, respectively one hour before HgCl2 administration for 3 days. Blood samples were taken by cardiac puncture and used for the measurement of urea and creatinine concentration. Twenty-hour-hour urine samples were collected to measure protein and glucose. The right kidney was fixed in formalin for histological examination and the left kidney was homogenized for measuring malondialdehyde (MDA) and total sulfhydryl groups. RESULTS: Significant elevation of serum creatinine and urea levels as well as urine glucose and protein concentrations, a significant decrease in total thiol content and a significant increase in MDA levels in kidney homogenate samples were observed after administration of HgCl2 as compared with control group. PSO pretreatment resulted in a significant decrease in serum creatinine and urea levels as well as urine glucose and protein concentrations when compared with HgCl2 treated (group II). PSO also significantly reversed the HgCl2-induced depletion in thiol content and elevation in MDA content. Histological studies revealed milder kidney lesions in PSO treated groups (groups III and IV) compared to HgCl2 treated group. CONCLUSION: Our results suggest that PSO has a protective effect against HgCl2-induced nephrotoxicity in rats.

Effect of pomegranate seed oil against gentamicin -induced nephrotoxicity in rat.

Gentamicin, an important aminoglycoside, is used to treat many types of bacterial infections, particularly those caused by Gram-negative organisms. It is a nephrotoxic antibiotic, which causes acute tubular necrosis, and its toxicity remains a major problem in clinical use. This study investigates the effect of pomegranate seed oil (PSO) on gentamicin-induced nephrotoxicity in adult male rats. Animals were randomly divided into four groups. Group one was treated with saline (1 ml/kg, i.p.), group 2 received gentamicin 80 mg/kg/day for 6 days and groups 3 and 4 received PSO 0.32 and 0.64 mg/kg/day i.p. respectively, 1 h before gentamicin. Serum urea, creatinine levels, urinary glucose and protein concentrations were evaluated as the markers of acute renal failure. Renal antioxidant indicators such as thiobarbituric acid-reactive substance (TBARS), and total thiol contents, were also determined. A significant elevation of serum creatinine and urea levels as well as urine glucose and protein concentrations were observed in gentamicin treated group. Gentamicin also caused a significant decrease in total thiol content and a significant increase in TBARS levels in kidney homogenate samples. PSO pretreatment resulted in a significant and dose-dependent decrease in serum creatinine and urea levels as well as urine glucose and protein concentrations when compared with gentamicin treated alone. PSO also significantly reversed the gentamicin-induced depletion in total thiol content and elevation in TBARS in kidney homogenate samples. The results of the present study indicate that PSO clearly attenuated gentamicin-induced nephrotoxicity, but elucidation of the mechanism(s) of this protection needs more investigation.

Effect of aqueous fraction of Rosa damascena on ileum contractile response of guinea pigs.

OBJECTIVE: The use of drugs with herbal origin is increasing for treatment of gastrointestinal (GI) disorders. Rosa damascena (R. damascena) is a well-known plant suggested to have beneficial effect on GI system. In this study, the effect of aqueous fraction of R. damascena on the contractions of isolated guinea pig ileum was investigated. MATERIALS AND METHODS: Aqueous fraction of plant was obtained from ethanolic extract after ethyl acetate and n-butanol fractions were discarded. To evaluate effect of this fraction on ileum contraction, guinea pig ileum was removed and mounted on organ bath and its contraction was recorded. Effect of various concentrations (0.66, 0.83, and 1.3 mg/ml) of aqueous fraction on ileum contraction in comparison with Ach in presence and absence of atropine, a muscarinic antagonist of cholinergic, was evaluated. The response of ileum to 1 µg/ml of acetylcholine was considered as 100% response. RESULTS: Our results showed that aqueous fractions of R. damascena dose-dependently increased basal guinea pigs ileum contractions (p<0.05 to p<0.001). Maximal contraction of fraction (1.3 mg/ml) induced 23.4 % of maximal Ach response. The contraction of ileum to aqueous fraction was significant decreased in presence 0.001 µg/ml of atropine. CONCLUSION: It is concluded that aqueous fraction of R. damascena has mild excitatory effect on ileum contraction and this fraction may be beneficial as a mild laxative agent.