Chikuni, Ordias (2005) “Organochlorine Pesticide Residues in Mothers’ Milk; Evaluation of Possible Drug Interaction in Humans”. PhD thesis, University of Zimbabwe.
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Abstract
The aim of the study was to investigate exposure levels of organochlorine pesticides (OCPs) in mother’s milk and in selected staple foods. The study also aimed to evaluated effects of 1,1,1- trochloro-2-bis-(4-chlorophenyl)ethane (DDT) on paracetamol half-life in highly exposed and least exposed breast-feeding mothers as a way of investigating possible drug interaction. This was an experimental study where milk and food samples from Esigodini, Harare, Kadoma Kariba Nyanga and Mudzi were collected and analysed for OCPs levels using GC-ECD. Evaluation of induction of the hepatic cytochrome P450 enzymes by DDT was carried out by pre-treatment of female rats with a single intraperitoneal dose of DDT (0.3 mg/g) body weight. Cytochrome P450 enzyme was quantified by potassium phosphate buffering the microsomal fraction followed by spectral determination of the reduction of cytochrome P450. Blood samples from selected mothers in areas showing results of higher exposure levels to DDT and selected mothers with low exposure levels to DDT (controls) were evaluated for paracetamol drug interaction. Concentration levels of paracetamol in rats were measured using UV-Visible spectrophotometry. Levels of paracetamol in human mothers were measured using the Immunochemistry System (ICS) based on immunochemical precipitation of paracetamol and nephelometric detection of the precipitate. The highest mean levels of DDT in mother’s milk were found in Mudzi with levels were16838.90 ng/g and the lowest was found in Esigodini with 934.12 ng/g. Results obtained from the analysis of hexachlorohexane (HCH) levels were comparably lower than DDT levels in the selected areas. There was a statistical significant correlation (r=0.8857, p= 0.0188) between DDT levels in staple food and mother’s milk. However, there was no statistical significant correlation (r=0.6571, p= 0.1562) between HCH levels in staple food and mother’s milk. Maximum induction of cytochrome P450 enzyme for test animals was at its highest (8.51 n mol /mg) on day 14 when compared to control animals, which had 0.55 n mol/mg at day 14. Hepatomegally was directly related to higher levels of cytochrome P450 in test animals while no liver enlargement was observed in control animals. DDT induced female rats and DDT exposed breast-feeding mothers showed interference with the pharmacokinetics of paracetamol at therapeutic dose level. The half-life of paracetamol in DDT pre-treated rats was 144 minutes when compared to control rats with 380 minutes a difference of 236 minutes. A similar trend was observed in the sampled breast-feeding mothers; analysis of the pharmacokinetic (half-life) data for highly DDT exposed mothers (212 minutes) and 13 least exposed (318 minutes), showed a significant difference (106 minutes) of paracetamol half-life. The conclusion from the study is that Kariba and Mudzi areas are highly exposed to DDT while Harare and Esigodini areas are least exposed. Exposure levels in breast milk are correlated to levels analysed in staple foods. Continued use of DDT for vector control is welcomed, but it should be done with intense monitoring to prevent long term effects of POPs on exposed individuals. More research is recommended so that scientists could assess the effects of the induction properties of OCPs on the efficacy, toxicity and the therapeutic index on dosage of many drugs used by animals and humans.
| Item Type: | Thesis (PhD) |
|---|---|
| Subjects: | R Medicine > RM Therapeutics. Pharmacology |
| Divisions: | Africana |
| Depositing User: | Geoffrey Obatsa |
| Date Deposited: | 24 Apr 2018 08:50 |
| Last Modified: | 24 Apr 2018 08:50 |
| URI: | http://thesisbank.jhia.ac.ke/id/eprint/3737 |
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