Ahmed Hakim

Polymorphism of the N-acetyltransferase 2 gene as a susceptibility risk factor for antituberculosis drug-induced hepatotoxicity in Tunisian patients with tuberculosis.

SETTING Antituberculosis drug-induced hepatitis attributed to isoniazide (INH) is one of the most prevalent drug-induced liver injuries. INH is metabolized by hepatic N-acetyltransferase 2 (NAT2) to form hepatotoxins. AIM To evaluate whether polymorphism of the NAT2 gene was associated with antituberculosis drug-induced hepatotoxicity in Tunisian patients. METHODS A total of 66 patients with tuberculosis (TB) who received anti-TB treatment were followed prospectively. Their NAT2 genotype was determined using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). We identified three single nucleotide polymorphisms (SNPs); 481C to T (NAT2*5B), 590G to A (NAT2*6A) and 857G to A (NAT2*7B). Univariate analysis and logistic regression analysis were used to evaluate the risk factors of isoniazid-induced hepatitis. RESULTS Fourteen patients (21.2%) were diagnosed with anti-TB drug-induced hepatitis. None of the rapid acetylators-type patients have expressed serum aminotransferase elevation. Among patients with hepatotoxicity, slow acetylators-type patients had a higher risk of hepatotoxicity than intermediate acetylators (21.4% vs. 78.6%, P=0.01). Statistical analysis revealed that the frequency of a variant diplotypes, NAT2*5B/5B and NAT2*6A/6A, were significantly increased in TB patients with hepatotoxicity, compared with those without hepatotoxicity (P=0.01, odds ratio [OR]=7.6 and P=0.029, OR=15, respectively). By contrast, the frequency of the rapid acetylation NAT2*4 allele was significantly lower in TB patients with hepatotoxicity than those without hepatotoxicity (P=0.02, OR=0.18). Moreover, 590G/G genotype was associated with decreased hepatotoxicity (P=0.01); by contrast, homozygous point mutation at position 481 and 590 were associated with a higher risk of hepatotoxicity (P=0.01). CONCLUSION Our results suggest that the slow-acetylator status of NAT2 is risk factor for INH-induced hepatotoxicity. Moreover, diplotypes, NAT2*5B/5B, NAT2*6A/6A, 481T/T and 590A/A, are useful new biomarkers for predicting anti-TB drug-induced hepatotoxicity.

Temporal specificity of training: intra-day effects on biochemical responses and Olympic-Weightlifting performances

Abstract The aim of this study was to investigate the performance of an Olympic-Weightlifting session training at three times of the day on the performance related to biochemical responses. Nine weightlifters (21 ± 0.5 years) performed, in randomised order, on three Olympic-Weightlifting training (snatch, clean and jerk) sessions (08:00 a.m., 02:00 p. m., 06:00 p. m.). Blood samples were collected: before, 3 min and 48 h after each training session. Haematological parameters and markers of muscle injury were assessed. Resting oral temperature and rating of perceived exertion (RPE) were also assessed during each session. ANOVA showed that the performance was better (P < 0.001) at 02:00 p. m. with a less RPE (P < 0.01) compared to the morning and the evening sessions while there was higher (P < 0.05) oral temperature at 06:00 p. m. versus 08:00 a.m. and 02:00 p. m. Muscle damage changed immediately (without significant effect after 48 h) after the training sessions with lower values in the evening compared to the morning. In conclusion, the afternoon training is more effective than morning or evening sessions for weightlifters. Therefore, coaches and weightlifters should be advised to schedule their training session in the afternoon hour.

Antioxidant status and oxidative stress at rest and in response to acute exercise in judokas and sedentary men.

El Abed, K, Rebai, H, Bloomer, RJ, Trabelsi, K, Masmoudi, L, Zbidi, A, Sahnoun, Z, Hakim, and A Tabka, Z. Antioxidant status and oxidative stress at rest and in response to acute exercise in judokas and sedentary men. J Strength Cond Res 25(9): 2400-2409, 2011. It is well recognized that acute strenuous exercise is accompanied by an increase in free-radical production and subsequent oxidative stress, in addition to changes in blood antioxidant status. Chronic exercise provides protection against exercise-induced oxidative stress by upregulating endogenous antioxidant defense systems. Little is known regarding the protective effect afforded by judo exercise. Therefore, we determined antioxidant and oxidative stress biomarkers at rest and in response to acute exercise in 10 competitive judokas and 10 sedentary subjects after mixed exercise (anaerobic followed by aerobic). The subjects performed a Wingate test, followed by 30 minutes of aerobic exercise performed at 60% of maximal aerobic power. Blood samples were taken, by an intravenous catheter, at rest (R), immediately after the physical exercise (P0), and at 5 (P5), 10 (P10), and 20 (P20) minutes postexercise. The measured parameters included the activity of the antioxidant enzymes superoxide dismutase, glutathione peroxidase, and glutathione reductase, in addition to α-tocopherol, and total antioxidant status. Malondialdehyde was measured as a representation of lipid peroxidation. At rest, the judokas had higher values for all antioxidant and oxidative stress markers as compared to the sedentary subjects (p < 0.05). Plasma concentrations of all parameters except for α-tocopherol increased significantly above resting values for both the judokas and sedentary subjects (p < 0.05) and remained elevated at 20 minutes postexercise. A significant postexercise decrease was observed for α-tocopherol (p < 0.05) at P20 for judokas and at P5 for sedentary subjects. These data indicate that competitive judo athletes have higher endogenous antioxidant protection compared to sedentary subjects. However, both groups of subjects experience an increase in exercise-induced oxidative stress that is not different.

Evaluation of efficacy of natural astaxanthin and vitamin E in prevention of colistin-induced nephrotoxicity in the rat model

OBJECTIVE We evaluated the effect of astaxanthin (ASX) and vitamin E (vit E) on colistin methanesulfonate (CMS) induced-nephrotoxicity in rats. METHODS Animals were treated with sterile saline, 300000 or 450 000 IU/kg/day of CMS, CMS + ASX (20 mg/kg), CMS + vit E (100 mg/kg), or CMS + 1 ml/kg olive oil (OO) for 7 days. The plasma/urine creatinine (Cr) level, urine γ-glutamyl-transferase (GGT) level, and renal tissue activities in malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and reductase (GSH), as well as renal histology were performed. RESULTS CMS induced a tubular damage, increased the GGT and MDA levels, and decreased the activities of SOD, CAT, GPx and GSH. Co-treatment with ASX or vit E restored all biochemical parameters cited above and improved the histopathological damage. CONCLUSION Nephrotoxicity induced by CMS might be due to oxidative damage. The improvement by ASX or vit E seems to be related to their antioxidant properties.

Protective effects of selenium on methimazole nephrotoxicity in adult rats and their offspring

This study aims to investigate the improving effects of selenium on methimazole-induced kidney impairments in adult rats and their pups. The animals were randomly divided into four groups of six each: group I served as control which received standard diet; group II received only methimazole in drinking water as 250 mg/l; group III received both methimazole (250 mg/l, orally) and selenium (0.5 mg/kg of diet); group IV served as a positive control and received selenium (0.5 mg/kg of diet) as sodium selenite (Na(2)SeO(3)). Treatments were started from the 14th day of pregnancy until day 14 after delivery. In the methimazole-treated group, body and absolute kidney weights decreased in pups and their mothers when compared to control. Daily urine volume, plasma creatinine levels were higher, while urinary levels were lower than in control. Besides, antioxidant enzyme activities, superoxide dismutase, catalase and glutathione peroxidase decreased. Lipid peroxidation recorded an increase revealed by high kidney malondialdehyde levels, while those of plasma and urinary uric acid showed a significant decline. Methimazole-treated rat kidneys exhibited leucocytic infiltrations, vascular congestion and narrowed Bowmans space. Co-administration of selenium through diet improved all the parameters cited above in adult rats and their progeny. Nevertheless, the distorted histoarchitecture in rat kidney was alleviated by selenium treatment. It can then be concluded that selenium is an important protective element that may be used as a dietary supplement against kidney impairments.

Dimethoate-induced oxidative damage in erythrocytes of female adult rats: possible protective effect of vitamin E and selenium supplemented to diet

Pesticide hazards have been accentuated by the sharp rise in their agricultural, industrial and domestic use. Acute exposure to pesticides can cause oxidative damage. Our study investigated the potential ability of selenium (Se) and/or vitamin E, used as nutritional supplements, to alleviate erythrocyte oxidative damage induced by dimethoate (DM), an organophosphate pesticide. Female Wistar rats were exposed to DM (0.2g/L−1 of drinking water), DM + Se (0.5 mg/kg of diet), DM + vitamin E (100 mg/kg of diet), or DM + Se + vitamin E. Rats exposed to DM for 30 days showed an increase in malondialdehyde levels, superoxide dismutase and glutathione peroxidase activities in their erythocytes, while Na+,K+-ATPase and catalase activities, glutathione, non-protein thiol, vitamin E and vitamin C levels decreased. We also noted an increase in lactate dehydrogenase activity, marker of haemolysis and a decrease in acetylcholinesterase, the principal mode of organophosphorus action. Co-administration of Se or vitamin E to the diet of DM-treated rats ameliorated the biochemical parameters cited above. But the combined effect of Se and vitamin E was more powerful in antagonizing DM-induced oxidative stress. Therefore, our investigation revealed that both Se and vitamin E were useful elements in preventing DM-induced erythrocytes damage.

Dimethoate Induced Oxidative Damage and Histopathological Changes in lung of Adult rats: Modulatory Effects of Selenium and/or Vitamin E

OBJECTIVE To determine the efficiency of selenium and/or vitamin E to alleviate lung oxidative damage induced by dimethoate, an organophosphorus compound. METHODS Adult Wistar rats were exposed during 30 days either to dimethoate (0.2 g/L of drinking water), dimethoate+selenium (0.5 mg/kg of diet), dimethoate+vitamin E (100 mg/kg of diet), or dimethoate+selenium+vitamin E. RESULTS Exposure to dimethoate caused oxidative stress in lung evidenced by an increase of malondialdehyde, protein carbonyl groups and advanced oxidation protein products. An increase in glutathione peroxidase, superoxide dismutase, catalase and a decrease in acetylcholinesterase and butyrylcholinesterase activities, glutathione, non-protein thiols and vitamins C levels were observed. Histopathological changes in lung tissue were noted as emphysema, hemorrhages and hemosiderin deposits. Co-administration of selenium or vitamin E to the diet of dimethoate treated rats ameliorated the biochemical parameters as well as histological impairments. The joint effect of these elements was more powerful in antagonizing dimethoate-induced lung oxidative damage. CONCLUSION We concluded that selenium and vitamin E ameliorated the toxic effects of this pesticide in lung tissue suggesting their role as potential antioxidants.

Evaluation of colistin nephrotoxicity administered at different doses in the rat model

Abstract Objective: This study evaluated the usefulness of plasma Cystatin C (pCysC) along with urinary neutrophil gelatinase-associated lipocalin (NGAL), γ-glutamyltransferase (GGT), lactate dehydrogenase (LDH), alkaline phosphatase (ALP), aspartate (AST) and alanine (ALT) aminotransferase to monitor colistin nephrotoxicity. Method: Male rats were given intramuscular (i.m.) injections of colistin in doses of 150,000 (G1), 300,000 (G2) and 450,000 IU/kg/day (G3) or normal saline (Control), every 12 h for 7 days. After the 14th injection, animals were placed in metabolic cages and urine samples were collected in the next 12 h. Thereafter, animals were euthanized, blood samples were collected and kidneys were removed for histological assessment. Results: Nephrotoxicity was completely dose-dependent according to pathologic findings. The major insults were acute tubular necrosis in the tubules of G3. No significant change in pCr was observed in all treated groups, but pCysC increased in the G3 compared to the control. In urinary markers, uNGAL level showed a dose dependant increase with significant change in the G2 and G3 groups compared to the control. However, there was no significant change in the AST, ALT, LDH or ALP activities but only GGT increased in the G3 compared to the control. Conclusion: Based on colistin doses used in our experimental study on rat model, histopathologic assessment remains the most accurate way to diagnose colistin nephrotoxicity. pCysC appears to be more reliable than pCr, and uNGAL seems to be the most sensitive factor of colistin nephrotoxicity.

Protective effects of selenium on methimazole-induced anemia and oxidative stress in adult rats and their offspring

The present study investigates the potential ability of selenium, considered as an antioxidant with pharmacological property to alleviate oxidative stress and hematological parameter disorders induced by methimazole, an antithyroid drug. Pregnant Wistar rats were randomly divided into four groups of six each: group I served as negative control and received a standard diet; group II received 250 mg/L of methimazole in drinking water and a standard diet; group III received both methimazole (250 mg/L, orally) and selenium (0.5 mg/kg of diet) supplemented to the standard diet; group IV served as positive control and received a supplement of selenium in the diet (0.5 mg/kg of diet) as sodium selenite (Na2SeO3). Treatment was started from the 14th day of pregnancy until day 14 after delivery. Methimazole reduced the number of red blood cells, hemoglobin concentration and hematocrit in mothers and their pups. Besides, plasma iron, vitamins B9, B12, C and E levels were reduced. Lipid peroxidation increased, objectified by high malondialdehyde levels and lactate dehydrogenase activity in plasma, while glutathione, glutathione peroxidase, superoxide dismutase and catalase activities showed a significant decline. Co-administration of selenium through diet improved all the parameters cited above. It can be concluded that the administration of selenium alleviates methimazole-induced toxicity, thus demonstrating its antioxidant efficacy.

Effect of fed- versus fasted state resistance training during Ramadan on body composition and selected metabolic parameters in bodybuilders

BackgroundMuslim bodybuilders often continue training during Ramadan. However, the effect of resistance training in a fasted versus a fed state during Ramadan on body composition and metabolic parameters in bodybuilders is not well known. The aim of this study was to evaluate the effects of resistance training in a fasted versus a fed state during Ramadan on body composition and metabolic parameters in bodybuilders.MethodsSixteen men were allocated to two groups: Eight practicing resistance training in the late afternoon in a fasted state (FAST), and eight training in the late evening in an acutely fed state (FED) during Ramadan. All visited the laboratory in the morning two days before the start of Ramadan (Bef-R) and on the 29th day of Ramadan (End-R) for anthropometric measurement, completion of a dietary questionnaire, and provision of fasting blood and urine samples.ResultsBody mass and body fat percentage remained unchanged in FAST and FED during the whole period of the investigation. Both FAST and FED experienced an increase in the following parameters from Bef-R to End-R: urine specific gravity (1%; p = 0.028, p = 0.004 respectively), serum concentrations of urea (4%, p = 0.006; 7%, p = 0.004 respectively), creatinine (5%, p = 0.015; 6%, p = 0.04 respectively), uric acid (17%; p < 0.001, p = 0.04 respectively), sodium (1%; p = 0.029, p = 0.019 respectively), chloride (2%; p = 0.039, p = 0.004 respectively), and high-density lipoprotein cholesterol (11%, p = 0.04; 10%, p = 0.04 respectively).ConclusionHypertrophic training in a fasted or in a fed state during Ramadan does not affect body mass and body composition of bodybuilders. Additionally, Ramadan fasting induced changes in urinary and some biochemical parameters, but these changes were not different according to when the training occurred.