СASE STUDY OF HEPATO-RENAL FAILURE IN A PATIENT AFTER ORTHOTOPIC HEART TRANSPLANTATION

Introduction. Heart transplantation remains the only radical treatment for end-stage heart failure (HF). Liver and / or renal dysfunction is common in patients with HF, which is also exacerbated by the use of artificial circulation and immunosuppressive therapy, and leads to postoperative complications and mortality. Case description. Patient P., 49 years old, after orthotopic heart transplantation was admitted to the intensive care unit (ICU) with signs of multiple organ failure. Graft rejection syndrome was suspected, but was not confirmed after the detailed clinical and laboratory examinations and according to the myocardial biopsy. Because of severe renal and hepatic insufficiency, patient at the ICU started to receive hemodiaultrafiltration with a flow of 190 ml/min; ultrafiltration – 100 ml/h. The condition, that developed was due to the direct effect of tacrolimus as the patient had a critically high plasma concentration of this drug (> 30 ng / ml) after the standard recommended postoperative dose (0.2 mg / kg per day). According to the literature, the elimination of the tacrolimus is provided by the liver, with microsomal cytochrome P450 3A4. Thus, the patient most likely had a failure of hepatic metabolism. Conclusion: Because of the systemic toxicity of tacrolimus, it is important to monitor its concentration after the first dose. Diagnosis of metabolic disorders at an early stage will prevent further systemic toxicity of tacrolimus. Efferent methods at ICU are the important tools for the correction of hepatic and renal insufficiency throughout toxic effects of tacrolimus.

In Vivo Modulation of Rat Liver Microsomal Cytochrome P450 Activity by Antimalarial, Anti-HIV, and Antituberculosis Plant Medicines

Drug interactions are key reasons for adverse drug reactions and attrition from market. Major infectious diseases causing morbidity/mortality in Ghana are malaria, tuberculosis, and HIV/AIDS. In this study, plant medicines commonly used to treat/manage these diseases in Ghana were investigated for their potential to modulate rat cytochrome P450 enzyme activities. Fluorescence and high-performance liquid chromatography–based assays were used to assess effects of antimalarial plant medicines, Fever (FEV), Mal-TF (MAL), and Kantinka terric (KT); anti-TB medicines, Chestico (CHES), CA + ST Pains + HWNT (TF), and Kantinka herbatic (KHB); and anti-HIV/AIDS medicines, Wabco (WAB), AD + T/AD (LIV) and Kantinka BA (KBA) on rat liver microsomal cytochrome P450 enzyme activities. Effects of medicines on rat biochemical and hematological parameters were also assessed. Generally, the medicines altered microsomal CYP1A1/1A2, CYP2B1/2B2, CYP2C9, and CYP2D6 activities. Only KBA elicited an increase (80%) in CYP1A1/1A2 activity. FEV, MAL, CHES, WAB, and LIV strongly inhibited the enzyme activity. All the medicines significantly inhibited CYP2C9 (24%-80%) activity. CYP2D6 activity increased after treatment with MAL, KBA, LIV, and TF. Also, MAL, WAB, LIV, KHB, and CHES increased CYP2B1/2B2 activity, while KT decrease the activity. Generally, the medicines altered liver function in the rats. Cholesterol levels declined after KBA treatment only. White and red blood cell counts, hemoglobin and hematocrit levels were significantly reduced in KT- and KBA-treated rats. Our results suggest that use of the medicines could have implications for drug interactions and safety, particularly if the medicines are administered over prolonged periods. Further investigations are imperative to establish clinical relevance of these results.

The acute toxicity of Oxydemeton-methyl in zebrafish

Oxydemeton-methyl, is an organothiophosphate insecticide, which is widely used in agricultural and urban pest controls. It exists in the environment and a large amount bioaccumulation in the wildlife due to its strong water solubility and mobility. Although its potentially harmful effect on animals and humans, few studies have focused on the oxydemeton-methyl pollution in the environment. Zebrafish have been used for many years to valuate the pollution status of water and toxicity of chemicals. In the present study, we aimed to investigate the effect of oxydemeton-methyl on the expression level of liver microsomal cytochrome P450, on the activity of NADPH-P450 reductase and reactive oxygen species (ROS) generation in zebrafish. Adult male and female zebrafish were treated with different concentration of oxydemeton-methyl (10, 50, 100 μM) for 5, 10, 20 and 30 days. We found that the oxydemeton-methyl exposure significantly increased the P450 levels and the activity of NAPDH-P450 reductase. ROS generation and the DNA damage were augmented in a dose-dependent manner in the zebrafish. These results indicated that oxydemeton-methyl is able to induce strong oxidative stress and hence highly toxic to the zebrafish.