Effects of Dichloromethane and N-Butanol Fractions of Nigella sativa on ACHN and GP-293 Cell Line Morphology, Viability, and Apoptosis.

Background: Renal cell carcinoma (RCC) is among the top death-causing cancers. Medicinal herbs can also have beneficial effects on RCC treatment. In this project, we aimed to study the antitumor effect of dichloromethane and N-butanol fractions of hydroalcoholic extract of Nigella sativa (N. sativa) on the morphology, viability, and apoptosis of ACHN (human renal adenocarcinoma) and GP-293 (normal renal epithelial) cell lines. Materials and Methods: In this experimental study, N-butanol and dichloromethane fractions of N. sativa were obtained, and ACHN and GP293 cell lines were treated with various concentrations of dichloromethane (0-100 µg/mL) and N-butanol (0-12.5 µg/mL) fractions for 24, 48, and 72 hours. Then, morphological changes, viability, and apoptosis were investigated. Results: Our results indicated that dichloromethane and N-butanol fractions cause morphological changes and significant decreases in the percentage of live cells in the ACHN cell line, in a dose- and time-dependent manner. In the GP-293 cell line, however, a lower toxicity was observed in comparison with that found for ACHN. The results of flow cytometry showed an apoptotic effect of dichloromethane and N-butanol fractions on the ACHN cell line but a higher rate of apoptosis induction for the total extract compared to the two fractions in the renal cancer cell line compared to the normal cell line. Conclusion: Our findings demonstrated that these two fractions of N. sativa induce inhibitory effects on the ACHN cell line morphology and viability. These effects were lower than those induced by the total extract. In addition, the two fractions caused more marked effects in the renal cancer cell line compared with the GP-293 cell line.

Association of indoor use of pesticides with CKD of unknown origin.

INTRODUCTION: Chronic kidney disease (CKD) is a growing global health problem. Recently, an epidemic of CKD of unknown origin (CKDu), a form of CKD seen mostly in agricultural communities, has been emerged. One of the proposed causes of CKDu is pesticide use in farmers. On the other hand, the research on relation between indoor use of pesticides and CKDu is little. In this study, we aimed to investigate the association between indoor use of pesticide as well as the exposure time with CKDu. This study was done as part of the population-based cohort of Prospective Epidemiological Research Studies in Iran. We used the baseline data of the Zahedan Adult Cohort Study. All subjects with diabetes mellitus and/or hypertension, estimated glomerular filtration rate (eGFR) between 60-89 ml/min/1.73 m2, and unavailable creatinine measurement were excluded. Subjects with an eGFR of less than 60 ml/min/1.73 m2 were defined as having CKDu, and their data were compared with those with an eGFR of more than 90 ml/min/1.73 m2. Data regarding indoor pesticide use and duration of exposure were obtained through a questionnaire. After applying the exclusion criteria, 1079 subjects remained in the study. Female sex, single marital status, low physical activity, triglyceride (TG) levels of more than 150 mg/dl, body mass index (BMI) of more than 25 kg/m2, non-smokers, indoor pesticide use, and high pesticide exposure time were associated with CKDu. The effects of age, female sex, TG levels more than 150 mg/dl, pesticide use (OR 1.36; 95% CI 1.01-1.84), and high exposure time (third tertile of exposure time) compared to non-users (OR 1.64; 95% CI 1.07-2.51) remained significant in multivariable analysis. CONCLUSION: We found a positive association between pesticide use, as well as longer exposure time to pesticides, and impaired kidney function in cases without diabetes mellitus and hypertension. Further longitudinal studies should be carried out to confirm these findings.

Downregulation of Profibrotic Gene Expression by Angiotensin Receptor Blockers.

INTRODUCTION: Chronic allograft nephropathy is characterized by interstitial fibrosis and tubular atrophy. The main players in the process of fibrosis are transforming growth factor-ß (TGF-ß) and miR-21 expression with a bidirectional interplay. This study aimed to evaluate the effects of angiotensin receptor type 1 antagonist, losartan, on peripheral blood and tissue expression of TGF-ß and miR-21 and histologic findings in allograft biopsy in kidney transplant recipients. MATERIALS AND METHODS: In a randomized controlled trial, 54 patients were enrolled and divided randomly into 2 groups. Group 1 was treated with a daily dose of 25 mg of losartan and group 2 was considered as control. Blood sampling was done at 48 hours posttransplantation and the 3rd and 6th months after transplantation for measurement of TGF-ß RNA and miR-21. Protocol biopsy was performed at the 6th month posttransplantation for RNA extraction and histologic evaluation of interstitial fibrosis and tubular atrophy. RESULTS: Although patients were not different initially, those who underwent treatment with losartan had lower miR-21 and TGF-ß levels in circulating PBMCs, and there was a decreasing trend in peripheral blood TGF-ß levels during the 6-month follow-up period. Tissue expression of miR-21 and TGF-ß was also considerably lower among the losartan-treated patients at the time of tissue biopsy. CONCLUSIONS: Losartan treatment decreased the tissue expression of miR-21 and TGF-ß and tissue fibrosis in kidney transplant patient, and it had a protective effect on allograft function and may delay chronic allograft dysfunction by reducing mediators of fibrosis.