Efeitos indesejáveis dos hipolipemiantes: condutas na prática clínica: [revisão] / Adverse effects of hypolipemic drugs: how to treat in clinical practice: [review]

Os fármacos hipolipemiantes, apesar de diminuírem a morbimortalidade por doença coronariana, não são destituídos de efeitos indesejáveis. Estes freqüentemente são transitórios, mas podem ocorrer alterações clínicas e laboratoriais que exigem especial atenção e diferentes condutas. Neste artigo, os autores relatam fundamentalmente como proceder diante do comprometimento muscular e hepático, considerados efeitos adversos mais relevantes dos hipolipemiantes. De modo sucinto, apontam os demais efeitos e a respectiva conduta.

Hypolipemic drugs improve coronary morbidity and mortality and appear to be safe; nevertheless appropriate monitoring is recommended. Adverse effects are reported that are frequently transitory. Severe adverse effects are infrequent, but clinicians must correctly screen them; symptoms and laboratory changes must be carefully interpreted. Often they call for special treatment and replacement of the hypolipemic drugs in use. This article emphasizes how to treat dyslipidemia if skeletal muscle and liver involvement are present. Briefly other adverse effects are also reported.

Effect of different doses of carotenoids in isoniazid-rifampicin induced hepatotoxicity in rats.

AIM: Isoniazid (INH) and Rifampicin (RIF) are hepatotoxic drugs. Oxidative stress has been reported as one of the mechanisms of INH+RIF induced hepatotoxicity. METHODS: Intragastric administration of INH and RIF (50 mg/kg body weight/day each) for 28 days in Wistar rats is hepatotoxic, indicated by raised transaminases and histology. Carotenoids have antioxidant properties. Therefore, different doses of carotenoids (2.5, 5, 10 and 20 mg/kg body weight/day) were administered to study the hepatoprotective effect against INH+RIF. RESULTS: The higher doses of carotenoids i.e.10 and 20 mg/kg body weight/day showed partial hepatoprotection indicated by return to normal of liver transaminase level and of liver histology in 33.3% of rats. There was no further protective effect seen by increasing the dose of carotenoids from 10 to 20 mg/kg body weight/day. Lower doses of carotenoids, i.e., 2.5 and 5 mg/kg body weight/day were not effective. CONCLUSION: Thus, a minimum dose with maximum hepatoprotection (10 mg/kg b.wt/ day) was selected as the optimum dose in the present study. The hepatoprotective nature of carotenoids in INH+RIF treated rats may be attributed to their antioxidative property.

Avaliação dos efeitos colaterais da nevirapina em gestantes HIV positivo em Hospital Universitário do sul do Brasil / Evaluation of the adverse effects of nevirapine in HIV-infected pregnant women in a South Brazilian University Hospital

OBJETIVO: avaliar a freqüência de efeitos advesos com o uso da nevirapina e suas correlações em gestantes infectadas pelo vírus da imunodeficiência humana (HIV). MÉTODOS: estudo retrospectivo foi realizado entre janeiro de 2003 e dezembro de 2006, incluindo todas as mulheres que utilizaram nevirapina durante a gestação. Os critérios de exclusão foram: início da nevirapina antes da gestação; presença de enzimas hepáticas basais aumentadas e dados incompletos de bioquímica hepática no prontuário. Os parâmetros avaliados foram idade, duração de exposição à nevirapina, idade gestacional no início da medicação, semanas de seguimento, carga viral, contagem de CD4 e dosagens de transaminases. A incidência de efeitos adversos hepáticos e/ou cutâneos foi determinada e correlacionada com a contagem de CD4. As análises estatísticas foram realizadas utilizando o teste exato de Fisher e o teste t de Student quando apropriado. A significância estatística foi estabelecida quando p<"0,05. RESULTADOS: cento e cinqüenta e sete gestantes foram incluídas nos critérios estabelecidos. Trinta e uma mulheres (19,7 por cento) apresentaram toxicidade cutânea e/ou hepática. Rash cutâneo foi responsável por 77,4 por cento das toxicidades e anormalidade da função hepática por 22,6 por cento. Hepatotoxicidades graus 1, 2 e 3 foram observadas em 0,6, 2,5 e 1,3 por cento, respectivamente. Contagem de CD4, carga viral e dosagem de transaminases basais foram similares em gestantes com e sem reação induzida pela nevirapina. A contagem de CD4 média foi de 465,4 e 416,6 células/µL em mulheres com e sem efeitos colaterais, respectivamente (p=0,3). Todas as pacientes que apresentaram hepatotoxicidade apresentavam contagem de CD4 prévia ao tratamento superior a 250 células/µL. CONCLUSÕES: a incidência de eventos adversos com nevirapina em nosso estudo foi alta, mas a maioria deles foi cutâneo. Não houve correlação entre a alta contagem de CD4 e os eventos adversos quando se analisou conjuntamente as reações cutâneas e hepáticas; entretanto, a hepatotoxicidade ocorreu apenas em gestantes com contagem de CD4 > 250 células/µL.

PURPOSE: The aim of this article is to evaluate the use of nevirapine HIV-infected pregnant women in our service. METHODS: a retrospective study was performed between January 2003 and December 2006 analysing all women prescribed nevirapine in pregnancy. Exclusion criteria included: (1) women who started nevirapine before pregnancy, (2) patients with abnormal baseline liver enzymes, and (3) women with incomplete liver biochemistry data. Evaluated parameters included age, weeks of exposure to nevirapine, gestational age in the begginning of medication, weeks of follow-up, viral load, CD4 cells count and serum aminotransferase levels. The incidence of adverse hepatic and/or cutaneous effects was determined and correlated to the CD4 cells count. Statistical analysis were performed using Fisher’s exact test and t-Student test when appropriate, with a statistical significance level of p<0,05. RESULTS: one hundred fifty-seven women met the inclusion criteria. Thirty-one (19.7 percent) presented cutaneous and/or hepatic toxicity. Skin rash accounted for 77.4 percent of toxicities and liver function abnormalities were noted in 22.6 percent of women exhibiting toxicities. Grade 1, 2 and 3 hepatotoxicities were observed in 0.6, 2.5 and 1.3 percent, respectively. Baseline CD4 counts, viral loads and transaminases were similar in pregnant women with nevirapine adverse effects and those without reaction. Median absolute CD4 cell counts were 465.4 and 416.6 cells/µL in women with and without side effects, respectively (p=0.3). All patients who experienced hepatotoxicity had pretreatment CD4 counts superior to 250 cells/µL. CONCLUSIONS: The incidence of adverse events with nevirapine in our study was high, but most of them were cutaneous. There was no correlation between high CD4 counts and adverse events when analysing both cutaneous and hepatic reactions; nevertheless, hepatotoxicity occurred only in pregnant women with CD4 counts >250 cells/µL.

Positive effects of Green Tea on hepatic dysfunction, lipid peroxidation and antioxidant defence depletion induced by cadmium

Cadmium (Cd) is a highly toxic environmental and industrial cumulative pollutant that affects many organs,especially the liver. The present study was designed to evaluate the antioxidant effect of green tea oncadmium-induced hepatic dysfunction and oxidative stress in rats. Adult male Wistar rats were administeredcadmium by injection of 20 ìmoles /kg bw/ every 3 days for six months. This study revealed significant (p <0.05) liver dysfunction, lipid peroxidation and a decline in antioxidant enzyme activities in the liver of cadmium-treated rats compared to control animals. Compared to control rats, the activities of lactate dehydrogenase (LDH), gammaglutamyl transferase (GGT), acid phosphatase (PAC), phosphatase alkaline (PAL), as well as bilirubin and thiobarbituric acid-reactive substances (TBARs), were significantly (p < 0.05)increased in Cd-treated rats. Moreover, antioxidant enzyme activities, such as superoxide dismutase (SOD), glutathione peroxidase (GPX) and catalase, were significantly (p < 0.05) decreased in the liver of cadmiumtreatedrats. The oral administration of 5% aqueous green tea extract, along with cadmium treatment for six months, caused a significant (p < 0.05) improvement in cadmium-induced toxicity by significantly decreasing(p < 0.05) the activities of enzymatic markers of liver dysfunction (LDH, GGT, PAC, PAL activities, as well as the bilirubin rate). Indeed, green tea extract significantly increased (p < 0.05) antioxidant enzymatic activities (SOD, Catalase, GPX) in rat liver, compared to those given cadmium alone. Thus, the oral administration of green tea, along with cadmium significantly (p < 0.05) improves cadmium-induced liverdysfunction and stress oxidant in rats’ liver.

experimental study on the impact of the Sudanese liquor [Aragi] in the etiology of liver damage

Alcoholism is considered as one of the life threatening problems due to its enormous effects on liver. To identify the biochemical and histological changes of Aragi on the liver of Wistar albino rats. It was conducted in fifteen adult male and female Wistar albino rats, five of which were slaughtered at day [zero] for histological investigation. The other ten rats were divided equally between the control and tested groups. The control was given water while the tested group was given Aragi for sixty days. The levels of glutamate oxaloacetate transaminase [GOT], glutamate pyruvate transaminase [GPT] and alkaline phosphatase [ALP] were measured at days[zero],[30] and [60] for both groups. Liver samples were investigated for histological changes at day [60] for both groups. The results revealed a statistically significant increase in the levels of ALP at day [30] [p<0.01], while GOT, GPT showed a significant increase at day [60] [p<0.01], as compared to the control. Histological findings of the livers of Aragi drinker rats, at day [60] revealed different grades of multinuclear cell infiltration, fibrosis, focal necrosis, fatty degeneration, as compared to the control and day [zero] groups, which showed no histological alteration. It was observed that three females of the control group gave birth to new offsprings during the sixty days of the experiment while none of the Aragi drinker females did. Aragi consumption plays a major role in liver damage which may lead to death, as well as impairment of fertility.

Effect of monothiol along with antioxidant against mercury-induced oxidative stress in rat.

Efficacy of thiol chelators viz. N-acetyl cysteine and D-penicillamine (NAC and DPA) along with nutritional supplements viz. zinc acetate, sodium selenite and magnesium sulphate (Zn, Se and Mg) in the treatment of mercury intoxication was investigated in rats. This is of particular interest since high bonding affinity between mercuric ion and the thiol group exits. The mutual antagonism of mercury and selenium is one of the strongest examples of the interaction in the trace element field. Adult rats of Sprague-Dawley strain were administered a bolus dose of dimethyl mercury (10 mg/kg) orally. A significant rise in the aspartate aminotransferase, alanine aminotransferase, serum alkaline phosphatase, lactate dehydrogenase, gamma glutamyltranspeptidase, bilirubin and creatinine were observed. Single mercury exposure also resulted in a significant increase in lipid peroxides with a concomitant decrease in reduced glutathione level in liver, kidney and brain. A decrease in the enzymatic activities of acetyl cholinesterase in different regions of the brain was observed. These parameters were restored considerably with chelating agents along with nutritional supplementation, but NAC+Se and DPA+Mg offered significant protection in comparison with other combinations.

Hepatoprotective effect of tocopherol against isoniazid and rifampicin induced hepatotoxicity in albino rabbits.

Antitubercular drug induced hepatotoxicity is a major hurdle for an effective treatment of tuberculosis. The present study was undertaken to assess the hepatoprotective potential of tocopherol (50 mg/kg and 100 mg/kg, ip) and to compare it with cimetidine (120 mg/kg, ip). Hepatotoxicity was produced by giving isoniazid (INH, 50 mg/kg, po) and rifampicin (RMP, 100 mg/kg, po) combination to albino rabbits for 7 days. Assessment of liver injury was done by estimating levels of alanine transaminase (ALT) and argininosuccinic acid lyase (ASAL) in serum and by histopathological examination of liver. Results revealed that pretreatment with high dose of tocopherol (100 mg/kg) prevented both biochemical as well as histopathological evidence of hepatic damage induced by INH and RMP combination. Moreover, tocopherol (100 mg/kg) was found to be a more effective hepatoprotective agent as compared to cimetidine.

Antioxidant DL-alpha lipoic acid as an attenuator of adriamycin induced hepatotoxicity in rat model.

Protective efficacy of DL-alpha lipoic acid on adriamycin induced hepatotoxicity was evaluated in rats. Adriamycin toxicity, induced by a single injection (ip; 15 mg/kg body wt), was expressed by an elevation in alanine transaminase, aspartate transaminase, bilirubin levels in serum and alkaline phosphatase, lactate dehydrogenase, alanine transaminase, aspartate transaminase activity in hepatic tissue. Adriamycin produced significant increase in malondialdehyde levels indicating tissue lipid peroxidation and potentially inhibiting the activity of antioxidant, reduced glutathione and antioxidant enzymes, catalase, superoxide dismutase, glutathione peroxidase, glutathione reductase, glutathione-S-transferase, glucose-6-phosphate dehydrogenase. The present results showed that pretreatment with lipoic acid [75 mg/kg body wt/day (ip), 24 h prior to administration of adriamycin] significantly restored various cellular activity suggesting the antioxidant potential of lipoic acid in ameliorating the hepatotoxicity induced by adriamycin.

Glycyrrhizin attenuates endotoxin- induced acute liver injury after partial hepatectomy in rats

Massive hepatectomy associated with infection induces liver dysfunction, or even multiple organ failure and death. Glycyrrhizin has been shown to exhibit anti-oxidant and anti-inflammatory activities. The aim of the present study was to investigate whether glycyrrhizin could attenuate endotoxin-induced acute liver injury after partial hepatectomy. Male Wistar rats (6 to 8 weeks old, weighing 200-250 g) were randomly assigned to three groups of 24 rats each: sham, saline and glycyrrhizin. Rats were injected intravenously with lipopolysaccharide (LPS) 24 h after 70 percent hepatectomy. Glycyrrhizin, pre-administered three times with 24 h intervals 48 h before hepatectomy, prolonged the survival of rats submitted to partial hepatectomy and LPS injection, compared with saline controls. Glycyrrhizin was shown to attenuate histological hepatic changes and significantly reduced serum levels of aspartate aminotransferase, alanine aminotransferase, and lactic dehydrogenase, at all the indicated times (6 rats from each were sacrificed 1, 3, 6, and 9 h after LPS injection), compared with saline controls. Glycyrrhizin also significantly inhibited hepatocyte apoptosis by down-regulating the expression of caspase-3 and inhibiting the release of cytochrome C from mitochondria into the cytoplasm. The anti-inflammatory activity of glycyrrhizin may rely on the inhibition of release of tumor necrosis factor-a, myeloperoxidase activity, and translocation of nuclear factor-kappa B into the nuclei. Glycyrrhizin also up-regulated the expression of proliferating cell nuclear antigen, implying that it might be able to promote regeneration of livers harmed by LPS. In summary, glycyrrhizin may represent a potent drug protecting the liver against endotoxin-induced injury, especially after massive hepatectomy.

Protective effect of Aquilegia vulgaris (L.) on carbon tetrachloride-induced oxidative stress in rats.

The ethyl ether extract of A. vulgaris inhibited in vitro microsomal lipid peroxidation (IC50 58.8 microg/ml) and showed moderate ability to scavenge superoxide radicals and to chelate iron ions. The extract (100 mg/kg body weight, po) decreased uninduced and enzymatic microsomal lipid peroxidation in the liver of male rats pretreated with CCl4 (1 ml/kg body weight) by 27 and 40%, respectively. Activity of antioxidant and related enzymes (catalase and glucose-6-phosphate dehydrogenase) inhibited by CCl4 was significantly restored after administration of the extract. The extract itself significantly enhanced superoxide dismutase activity. There was no effect of the extract on hepatic glutathione level and cytochrome P450 content, both were decreased by CCl4. Neither CCl4 nor the tested extract affected activities of NADPH-cytochrome P450 reductase and two monooxygenases, aniline hydroxylase and aminopyrine n-demethylase. It can be concluded that the protective effect of the A. vulgaris extract in CCl4-induced liver injury is mediated by inhibition of microsomal lipid peroxidation and restoring activity of some antioxidant and related enzymes.

Análise morfológica dos fígados e rins no binômio materno-fetal após tratamento de ratas prenhes com Ritonavir durante toda a prenhez / Morphological analysis of liver and kidneys of pregnant rats and their fetuses upon chronic Ritonavir administration

OBJETIVO: avaliar os efeitos da administração crônica de três diferentes doses de Ritonavir nos fígados e rins de ratas prenhes e seus conceptos do ponto de vista morfológico. MÉTODOS: Quarenta ratas albinas EPM-1 Wistar, prenhes, foram aleatoriamente divididas em quatro grupos: Contr (controle do veículo) e três grupos experimentais, Exp20, Exp60 e Exp180, que receberam, respectivamente, 20, 60 e 180 mg/kg por dia de Ritonavir por via oral. A droga e o veículo (propilenoglicol) foram administrados por gavagem, desde o primeiro até o 20º dia da prenhez. No último dia do experimento, todos os animais foram anestesiados e sacrificados. Em seguida, fragmentos dos fígados e rins maternos e fetais foram coletados e preparados para análise em microscopia de luz. RESULTADOS: não observamos nenhuma alteração morfológica nas vísceras estudadas nos Grupos Contr e Exp20. No Grupo Exp60, encontramos, no fígado materno, hepatócitos com sinais de atrofia e de apoptose (eosinofilia citoplasmática e núcleos picnóticos) e vasodilatação marcante dos capilares sinusóides (congestão). No rim materno, encontramos áreas eosinofílicas e núcleos hipercromáticos na parede dos túbulos contorcidos proximais. O fígado e rins maternos do Grupo Exp180 tiveram alterações morfológicas mais intensas do que no Grupo Exp60. Não observamos alterações histomorfológicas nos fígados e rins fetais em todos os grupos, o que pode ser decorrente da ação protetora da glicoproteína P. CONCLUSÕES: nossos resultados mostram que a administração de Ritonavir a ratas prenhes causou alterações morfológicas nos fígados e rins maternos em doses mais altas que a convencional. Já a ausência de anormalidades nos órgãos fetais pode ser explicada pelo papel protetor da glicoproteína P.

PURPOSE: to evaluate the effect of the chronic administration of three different doses of Ritonavir in the liver and kidneys of pregnant albino rats and their concepts from a morphological standpoint. METHODS: forty pregnant albino EPM-1 Wistar rats were randomly divided into four groups: Contr (vehicle control), and three experimental groups, Exp20, Exp60, Exp180, which received daily 20, 60 or 180 mg/kg of Ritonavir, respectively. The drug and the vehicle (propyleneglycol) were orally administered by gavage, from the first up to the 20th day of pregnancy. At the last experimental day, all the animals were sacrificed under deep anesthesia, and fragments from the maternal and fetal liver and kidneys were taken and prepared for histological analysis by light microscope. RESULTS: no morphological changes were identified in Exp20 and control group. In the Exp60 group, we found hepatocytes with signs of atrophy and apoptosis (eosinophilic cytoplasm and picnotic nuclei) and marked sinusoid capillary vasodilation (congestion). The proximal convoluted tubules of maternal kidneys and liver showed eosinophilic areas and hyperchromatic nuclei, as well as signs of vasodilation. The maternal kidneys and livers of the Exp180 rats presented more prominent morphological changes than the ones of Exp60. Regarding the fetal organs, no histomorphological abnormalities were observed in all the groups. CONCLUSIONS: our results show that the administration of Ritonavir to pregnant rats, in higher than conventional doses causes morphological changes in the maternal liver and kidneys. On the other hand, the lack of abnormalities in the fetal organs may be due to the protective role of glycoprotein P.

Evaluation of hepatoprotective activity of Clerodendrum serratum L.

The ethanol extract of C. serratum roots and ursolic acid isolated from it were evaluated for hepatoprotective activity against carbon tetrachloride induced toxicity in male Wistar strain rats. The parameters studied were estimation of liver function serum markers such as serum total bilirubin, total protein, alanine transaminase, aspartate transaminase and alkaline phosphatase activities. The ursolic acid showed more significant hepatoprotective activity than crude extract. The histological profile of the liver tissue of the root extract and ursolic acid treated animal showed the presence of normal hepatic cords, absence of necrosis and fatty infiltration as similar to the controls. The results when compared with the standard drug silymarin, revealed that the hepatoprotective activity of the constituent ursolic acid is significant as similar to the standard drug.

Cassia occidentalis poisoning as the probable cause of hepatomyoencephalopathy in children in western Uttar Pradesh.

BACKGROUND & OBJECTIVE: Recurrent annual outbreaks of acute encephalopathy illness affecting young children have been reported for several years in many districts of western Uttar Pradesh (UP). Our earlier investigations over three consecutive years (2002-2005) proved that these outbreaks were due to a fatal multi-system disease (hepatomyoencephalopathy syndrome) probably caused by some phytotoxin and not due to viral encephalitis as believed so far. We conducted a case-control study to investigate the risk, if any, from various environmental factors and also to identify the putative toxic plant responsible for development of this syndrome. METHODS: Eighteen cases with acute hepatomyoencephalopathy syndrome admitted in 2005 in a secondary care paediatric hospital of Bijnor district of western UP were included in the study. Three age-matched controls were selected for each case. A semi-structured questionnaire was developed and applied to all 18 cases and 54 controls. All interviews were conducted within one week of discharge or death of each case. Quantitative data were analyzed using the relevant established statistical tests. RESULTS: Parents of 8 (44.4%) cases gave a definite history of their children eating beans of Cassia occidentalis weed before falling ill, compared with 3 (5.6% controls), the odds ratio being 12.9 (95% CI 2.6-88.8, P<0.001). History of pica was the other associated factor with the disease, odds ratio 5.20 (95% CI 1.4-19.5, P<0.01). No other factor was found significantly associated with the disease. INTERPRETATION & CONCLUSION: Consumption of C. occidentalis beans probably caused these outbreaks, described earlier as hepatomyoencephalopathy syndrome. Public education has the potential to prevent future outbreaks.

Reduction of hexachlorocyclohexane-induced oxidative stress and cytotoxicity in rat liver by Emblica officinalis gaertn.

The effect of prefeeding of dehydrated E. officinalis (amla) powder at 5 and 10% levels on hexachlorocyclohexane (HCH)-induced changes in multicomponent antioxidant system and lipid peroxides in rat liver was studied. HCH induced significant elevation in hepatic malondialdehyde, conjugated dienes and hydroperoxides. The prefeeding of amla at 10% level could decrease the formation of these lipid peroxides significantly. The HCH abuse resulted in a significant reduction in hepatic glutathione S-transferase (GST), glucose-6-phosphate dehydrogenase (G-6-PDH) and superoxide dismutase (SOD) activities with an elevation in the activities of glutathione peroxidase and gamma-glutamyl transpeptidase (GGT). On the other hand, the HCH-induced impairment in hepatic catalase, G-6-PDH and SOD activities were modulated by amla at the 10% level of intake. Prefeeding of amla at 5 and 10% levels appeared to reduce the HCH-induced raise in renal GGT activity. The results show the elevation of hepatic antioxidant system and reduction of cytotoxic products as a result of prefeeding of amla, which were otherwise affected by the HCH administration.

Radical scavenging activity of Trianthema triquetra in male albino rats intoxicated with CCl4.

Radical scavenging activity of ethanolic extract of Trianthema triquetra root was investigated against CCl4 in rats. The rats were treated with T. triquetra (100 mg, 200 mg/kg b.w.) for a period of 7 days. Antihepatotoxic effect was studied by assaying the activities of thiobarbituric acid (TBARS), reduced glutathione (GSH), glutathione peroxidase (GPx),catalase (CAT), super oxide dismutase (SOD) and vitamin C (Vit. C). Lipid peroxidation is evidenced by an increase in the value of TBARS and also a distinct diminution in the level of GSH, Vit. C at 200 mg/kg b.w. The activity of antioxidant enzymes, such as GPx, CAT SOD and Vit. E is significantly recovered towards an almost normal level in animals coadministrated with T. triquetra. The maximum protection against CCl4 induced hepatic injury was afforded by the dose of 200 mg/kg b.w. of Trianthema triquetra.

Screening of hepatoprotective effect of a herbal mixture against CCl4 induced hepatotoxicity in Swiss albino mice.

The hepatoprotective potential of a herbal mixture was evaluated against CCl4 induced liver injury in Swiss albino mice. Liv 52, a commercially available polyherbal hepatoprotective drug was evaluated for comparison. The potential toxicity of the above herbal hepatoprotective agents was also compared. It was observed that there was a reduction in the enzyme biomarkers (Aspartate and Alanine Transaminase) of liver injury in the herbal mixture treated groups, which was similar to the reduction initiated by Liv 52. An increase in glutathione was observed in the herbal mixture treated groups and it was assumed that the herbal mixture protects the liver by virtue of its antioxidant nature along with high regeneration initiation potential. From the study it is also concluded that the herbal mixture is safer than Liv 52.

Impediment of diethylnitrosamine induced hepatotoxicity in male Balb/c mice by pretreatment with aqueous Azadirachta indica leaf extract.

Considering the hepatoprotective properties of Azadirachta indica, the present study was designed to evaluate its preventive effects against diethylnitrosamine (NDEA) induced hepatotoxicity in male Balb/c mice. Exposure of NDEA caused a significant increase in micronucleated cell score, lipid peroxidation levels (LPO) and activity of lactate dehydrogenase (LDH). A significant decrease in reduced glutathione (GSH) contents and activity of glutathione-S-transferase (GST) was also observed upon NDEA treatment, whereas their activities of cytochrome P450 and cytochrome b5 showed non-significant alterations. Aqueous A. indica leaf extract (AAILE) pretreatment showed protective effects against NDEA induced toxicity by decreasing the frequency of micronucleated cell, levels of LPO and LDH activity. Also, a decreased activity of GST, cytochrome P450 and an increased activity of cytochrome b5, GSH contents was observed when AAILE pretreated mice were injected with NDEA. Only AAILE treatment caused a noticeable decrease in the frequency of micronuclei, activity of cytochrome P450 and cytochrome b5, but a significant increase in the activity of GST and GSH contents, whereas, non significant alterations were observed in the activity of LDH and levels of LPO. Significance of these observations with respect to hepatoprotective efficacy of A. indica has been discussed in the present manuscript.

Alfuzosin-induced Acute Liver Injury / 대한간학회지

We describe a 56-year-old man who developed an acute liver injury after taking alfuzosin for 1 month to control his newly diagnosed benign prostatic hypertrophy (BPH). There was no history of alcohol consumption or the taking herbal or traditional remedies. Viral causes, autoimmune hepatitis, and biliary tree obstruction were excluded. Other rare causes of hepatitis such as hemochromatosis, primary biliary cirrhosis and Wilson's disease were also absent in this patient. His liver test results began to improve after discontinuing the alfuzosin. Two weeks later, alfuzosin was administered again because the patient complained of dysuria. After 10 days of alfuzosin reuse, his liver test results worsened. Five months later after the complete discontinuation of the drug, his liver test results had returned to normal. This clinical sequence suggests that alfuzosin caused his acute liver injury.

Generalized Pustular Psoriasis and Hepatic Dysfunction Associated with Oral Terbinafine Therapy

We report a case of 61-yr-old man with stable psoriasis who progressively developed generalized pustular eruption, erythroderma, fever, and hepatic dysfunction following oral terbinafine. Skin biopsy was compatible with pustular psoriasis. After discontinuation of terbinafine and initiating topical corticosteroid and calcipotriol combination with narrow band ultraviolet B therapy, patient's condition slowly improved until complete remission was reached 2 weeks later. The diagnosis of generalized pustular psoriasis (GPP) induced by oral terbinafine was made. To our knowledge, this is the first report of GPP accompanied by hepatic dysfunction associated with oral terbinafine therapy.