Inflammatory bowel disease and drug-induced liver damage

The article presents the results of a review of publications devoted to the study of the problems of drug-induced liver damage in inflammatory bowel diseases (IBD). The hepatotoxic effect of thiopurines (azathioprine and 6-mercaptopurine) — hepatotoxicity from 0% to 17%; sulfasalazine and mesalamine (hepatotoxicity from 0% to 4%); methotrexate (hepatotoxicity from 15% to 50%); tumor necrosis factor inhibitors (hepatotoxicity up to 75% of cases.), anti-integrins (hepatotoxicity from 2% to 5%); an interleukin 12/23 inhibitor (hepatotoxicity from 0,5% to 2%); Janus-kinase inhibitors is considered (hepatotoxicity from 1% to 2%).Conclusion. The drugs currently used to treat IBD require periodic liver function tests to rule out drug-induced lesions that require therapy correction. As the range of new drugs is rapidly expanding, this requires special observation and discussion in terms of their adverse effects on the liver.

Аcute paracetamol intoxication

Paracetamol is non-narcotic analgesic and antipyretic of the central action from group of anilides, widely used in clinical practice. This drug has pronounced hepatotoxic effect which amplifies with alcohol. Paracetamol intoxication most frequently happens as a result of deliberate peroral intake of excessive doses of drug with a suicidal purpose. Undeliberate medicine poisoning is possible as a result of self-treatment.

Astaxanthin Mitigates Thiacloprid-Induced Liver Injury and Immunotoxicity in Male Rats

Thiacloprid (TCP) is a widely used neonicotinoid insecticide with a probable toxic hazard to animals and human beings. This hazard has intensified the demand for natural compounds to alleviate the expected toxic insults. This study aimed at determining whether astaxanthin (ASX) could mitigate the hepatotoxic effect of TCP and diminish its suppressive effect on immune responses in rats. Animals received TCP by gavage at 62.1 mg/kg (1/10th LD50) with or without ASX at 40 mg/kg for 60 days. Intoxicated rats showed modulation of serum transaminases and protein profiles. The hemagglutination antibody titer to sheep red blood cells (SRBC) and the number of plaque-forming cells in the spleen were reduced. The cell-mediated immunity and phagocytosis were suppressed, while serum interleukins IL-1β, IL-6, and IL-10 were elevated. Additionally, malondialdehyde, nitric oxide, and 8-hydroxy-2′-deoxyguanosine levels were increased in the liver, spleen, and thymus, with depletion of glutathione and suppression of superoxide dismutase and catalase activities. The expressions of inducible nitric oxide synthase and the high mobility group box protein 1 genes were upregulated with histomorphological alterations in the aforementioned organs. Cotreatment with ASX markedly ameliorated the toxic effects of TCP, and all markers showed a regression trend towards control values. Collectively, our data suggest that the protective effects of ASX on the liver and immune system of TCP-treated animals depend upon improving the antioxidant status and relieving the inflammatory response, and thus it may be used as a promising therapeutic agent to provide superior hepato- and immunoprotection.

Anti-Hepatotoxic Effect of Vananimbuka (Glycosmis pentaphylla Retz.)

Liver, one of the largest of organs and a chief site for intense metabolism and excretion. It has a surprising role in the maintenance, performance and regulating homeostasis of the body. The major functions of liver are carbohydrate, protein, and fat metabolism, detoxification, secretion of bile and storage of vitamin. Maintaining a healthy liver is a crucial factor for overall health and well-being. But it is continuously and frequently exposed to environmental toxins, abused by poor food habits and alcohol. Prescribed and over-the-counter drugs can eventually lead to various liver ailments like hepatitis and liver cirrhosis. Thus liver diseases are some of the fatal health issues in the world today. According to Ayurveda, Yakrut is considered as one of the 15 koshtangas. It is also considered as sthana of ranjaka pitta and plays an important role in maintenance of agni. Hepatic disorders can be compared to yakrut vikaras and yakrutpleeha vikaras. In ayurveda Vananimbuka discribtion is available for yakrut vikara.

Histopathological Changes in Liver Tissue after repeated administrations of an Intermediate Dose of Coenzyme Q10 to Wistar Rats

Coenzyme Q10 (Co-Q10) or ubiquinone plays an important role in the cellular metabolism. The safety profile of ubiquinone as a dietary supplement has been assessed in few sub-chronic toxicity studies. The aim of this study was to evaluate the possible hepatotoxic effect of long-term oral administration of an intermediate oral dose of Co-Q10 in experimental animals. Fifteen Wistar rats were treated with 300mg/kg daily oral doses of Co-Q10 using forced oral feeding for six weeks. Additional 5 healthy rats represented the control group for comparison. All rats were euthanized at the end of the 6th week. Then H and E stained histological sections of rats’ livers revealed vacuolation of hepatocytes, an increase in the diffusion of macrophages and the formation of microgranuloma most probably indicating a drug-induced injury. In conclusion, this study adds evidence supporting the potential hepatotoxic actions resulting from repeated administration of intermediate oral dose of Co-Q10 especially on the long-term.

Detraction of Diclofenac-Associated Hepatotoxicity by Fresh Beet Root Juice in Male Albino Mice

The beet root as dietary supplement hepatoprotective ability has gained interest in recent days. The present study was designed to determine the potential hepatoprotective effect of beet root juice as anti-inflammatory and anti-oxidant agent to eliminate the hepatotoxic effect of diclofenac as wide spread analgesic agent. Male albino mice were divided randomly into 4 groups, the 1st group served as control group, the 2nd group received 8 mL/kg of freshly prepared beet root juice, the 3rd group received oral administration 20 mg/kg of diclofenac and the 4th group pre-treated with beet root before one-hour diclofenac administration for 30 days. Biochemical results revealed sharp significant raised levels of liver enzymes level (AST, ALT, ALP and GGT) in the 3rd group that received diclofenac, besides to marked pathological changes manifested by high pathological scoring system such as hepatocytes degeneration, ballooning, infiltration and fibrosis. Immunohistochemical analysis elucidated massive incidence of MDA as an indicator of oxidative stress, moreover great number of neutrophils were seen as main component of inflammation. Whereas, pre-treatment of beet root juice one hour before diclofenac resulted in significant decrease of liver enzymes, clear attenuation of pathological features, decrease of pathological score. A great reduction of MDA in liver tissue and number of neutrophils stained histochemically. It was concluded that beet root juice possessed beneficial hepatoprotective role against diclofenac, as significant anti-oxidant and anti-inflammatory effect.

Efek Hepatotoksisitas Tanaman Obat

The utilization of medicinal plants in Indonesia has been going on for generations even before modern medicine began to be marketed. Although its properties are widely known, but certain medicinal plants can give toxic effects to the liver. This study was aimed to re-evaluate the hepatotoxic effects of medicinal plants and changes in liver morphology. This was a literature review study using databases of Pubmed, ClinicalKey, and Google Scholar. The results obtained five medicinal plants that had hepatotoxic effects. Areca catechu showed morphological changes in the form of hemorrhagic, sinusoid dilation, lobular inflammation, lobular disarray, necrosis, interface hepatitis, microsteatosis, hepatocellular cholestasis, and steatosis. Myrmecodia pendans showed the presence of fat degeneration, necrosis, and inflammatory cell infiltration. Annona muricata indicated the presence of hepatocyte swelling. Gynura divaricata showed increases of SGOT and SGPT levels. Vernonia amygdalina Del showed the presence of cellular degeneration and necrosis of hepatocytes. In conclusion, the most diverse morphological changes of liver are caused by Areca catechu along with large dose consumption meanwhile the most minimal morphological changes of the liver are caused by Annona muricata.Keywords: herbal medicine; hepatotoxic effect Abstrak: Pemanfaatan tanaman obat di Indonesia telah berlangsung selama turun-temurun bahkan sebelum obat modern mulai dipasarkan. Meskipun khasiatnya telah banyak diketahui, namun tanaman obat tertentu dapat memberikan efek toksik pada hati. Penelitian ini bertujuan untuk mengevaluasi kembali efek hepatotoksik tanaman obat dan perubahan morfologik hati. Jenis penelitian ialah literature review, menggunakan database Pubmed, ClinicalKey, dan Google Scholar. Hasil penelitian ini mendapatkan lima jenis tanaman obat yang bersifat hepatotoksik. Areca catechu menunjukkan adanya perubahan morfologik berupa perdarahan, dilatasi sinusoid, inflamasi lobular, lobular disarray, nekrosis, interface hepatitis, mikrosteatosis, kolestasis hepatoseluler, dan steatosis. Myrmecodia pendans menunjukkan adanya degenerasi lemak, nekrosis, dan infiltrasi sel radang. Annona muricata menunjukkan adanya pembengkakan hepatosit. Gynura divaricata menunjukkan adanya peningkatan kadar SGOT dan SGPT. Vernonia amygdalina Del menunjukkan adanya degenerasi dan nekrosis hepatosit. Simpulan penelitian ini ialah perubahan morfologik hati yang paling beragam disebabkan oleh Areca catechu seiring dengan besar dosis yang dikonsumsi sedangkan perubahan morfologik hati yang paling minimal disebabkan oleh Annona muricata.Kata kunci: tanaman obat; efek hepatotoksik

Liver Profile of Artemether-lumefantrine-tinidazole in Healthy and Parasitized Mice

Artemether/lumefantrine/tinidazole (A/L/T) has shown additive antiplasmodial activity; therefore its safety assessment is imperative. This study examined its hepatotoxic effect on healthy and diseased mice. Fifty four Swiss albino mice of n=6 were used. The mice were diseased with Plasmodium berghei ( ) and treated with T (28.6 mg/kg), A/L (2.3/13.7mg/kg) and A/L/T for 4 days, respectively. Healthy mice were treated with T (28.6 mg/kg), A/L (2.3/13.7mg/kg) and A/L/T for 28 days, respectively. After drug treatment; the mice were weighed and anesthetized. Liver samples were excised, weighed and evaluated for oxidative stress indices and histology. Blood samples were assessed for serum liver function indices. Treatment with T, A/L and A/L/T produced no significant (p>0.05) effects on all evaluated parameters in parasitized mice when compared to control. Significant decrease in body weight with significant increase in liver weight occurred in healthy mice treated with A/L (p<0.05) and A/L/T (p<0.01) when compared to control. Impaired liver function characterized by significantly increased serum aminotranferases, alkaline phosphatase, lactate dehydrogenase, gamma-glutamyl transferase, and bilirubin levels with significantly decreased total protein and albumin levels occurred in healthy mice treated with T (p<0.05), A/L (p<0.01) and A/L/T (p<0.001) when compared to control. Significantly decreased glutathione peroxidase, superoxide dismutase, glutathione, and catalase levels with significantly increased malondialdehyde levels occurred in healthy mice treated with T (p<0.05), A/L (p<0.01) and A/L/T (p<0.001) when compared to control. A/L/T caused hepatocyte necrosis in healthy mice. The use of A/L/T for malaria treatment seems safe on the liver, but may impair liver function with prolonged use.