dieldrin and Necrosis

Dieldrin, an organochlorine pesticide still used in several developing countries, has been proposed as a risk factor for Parkinson's disease. Quercetin is one of the potent bioactive flavonoids present in numerous plants. In this study, we investigated the protective effects of quercetin on neurotoxicity induced by dieldrin in cultured dopaminergic SN4741 cells. Our initial experiments showed that quercetin (10-40 μM) dose dependently prevented dieldrin (20 μM)-induced cytotoxicity in SN4741 cells. Pretreatment for 1 h with quercetin before dieldrin application could significantly suppress dieldrin-induced apoptotic characteristics, including nuclear condensation, DNA fragmentation, and caspase-3/7 activation. Results showed that dieldrin-induced markers of endoplasmic reticulum (ER) stress response such as chaperone GRP78, heme oxygenase-1, and phosphorylation of the α subunit of eukaryotic initiation factor 2. In addition, dieldrin reduced antiapoptotic Bcl-2 expression, but significantly elevated a proapoptotic transcription factor CHOP. Furthermore, RNA interference to CHOP almost completely repressed dieldrin-induced apoptotic cell death. Interestingly, quercetin prevented the changes in dieldrin-induced ER stress markers. These results suggest that quercetin may suppress the ER stress-CHOP pathway and dieldrin-induced apoptosis in dopaminergic neurons.

Topics: Animals; Apoptosis; Caspases; Cell Line; Dieldrin; DNA Fragmentation; Dopaminergic Neurons; Dose-Response Relationship, Drug; Endoplasmic Reticulum Chaperone BiP; Endoplasmic Reticulum Stress; Eukaryotic Initiation Factor-2; Heat-Shock Proteins; Heme Oxygenase-1; L-Lactate Dehydrogenase; Membrane Proteins; Mice; Necrosis; Neuroprotective Agents; Proto-Oncogene Proteins c-bcl-2; Quercetin; RNA, Small Interfering; Transcription Factor CHOP

Renal lesions developed in Osborne-Mendel male and female rats ingesting dieldrin or aldrin in the diet. Chronic interstitial nephritis was seen in rats surviving for 52 wk or longer. The incidence of nephritis was highest and the lesion was most severe in male rats given the higher dose levels of dieldrin, 50 ppm or higher. Over one-half of the rats fed dieldrin or aldrin at 150 ppm, and many fed 100 ppm, died from renal necrosis and sometimes hepatic necrosis during the first year. More female rats died from renal necrosis than did male rats. Rats dying from renal necrosis did not develop tumors; those from severe chronic nephritis either did not have tumors or had preneoplastic lesions that would have become tumors if the animal had lived longer. Thus acute and chronic effects should both be examined carefully when evaluating the safety of a chemical. In addition to causing the death of the animal, acute and chronic toxic effects can prevent the development of malignant tumors by shortening the animal's life span or by causing illness and inhibiting the development of a tumor that otherwise might occur in a healthy animal.

Topics: Aldrin; Animals; Dieldrin; Female; Kidney; Kidney Diseases; Kidney Neoplasms; Male; Necrosis; Nephritis; Rats; Sex Factors

Topics: Animals; Body Weight; Brain; Dehydration; Dieldrin; Dietary Proteins; Kidney; Liver; Male; Necrosis; Pesticides; Protein Deficiency; Rats; Regional Blood Flow; Seizures; Stress, Physiological