Please use this identifier to cite or link to this item: http://hdl.handle.net/123456789/567
Title: BIOACCUMULATION, BIOTOXICITY AND BIODEGRADATION OF FENVALERATE IN RATS
Authors: Misra, Swati
Keywords: BIOACCUMULATION
BIOTOXICITY
BIODEGRADATION
FENVALERATE IN RATS
Issue Date: 1995
Abstract: Fenvalerate, [1, cyano (3-phenoxyphenyl) methyl 4-chloro-a-(l-methylethyl) benzeneacetate, Pydrin insecticide], a synthetic pyrethroid is widely used now a days to control a range of pests. In the present study bioaccumulation, biodegradation and biotoxicity of fenvalerate was investigated in liver, kidney and brain, at both cellular and subcellular levels, in rats exposed to acute and chronic treatments. In acute treatment after 6, 1'2, 24, 36 and 48 h of oral administration of a single dose (100 mg/Kg body weight), the organs were removed and analysed by HPLC for residual pesticide and its metabolites. Pattern'of biodegradation of pesticide as judged by HPLC data was found to be nearly identical in liver, kidney and brain, except the rapid degradation of the pesticide (about 98% in 48 h) in liver compared to that in kidney and brain where the degradation was 78% and 68% respectively. Two metabolites designated as PI and PII were formed. These were isolated in pure form by repeated HPLC and identified by IR spectroscopy as (4-chloro-a-(l-methylethyl) benzeneacetic acid] and 3-phenoxybenzoic acid respectively. The bioaccumulation pattern of fenvalerate and its metabolites was also studied under chronic toxicity after administering repeated oral doses of 5 mg/Kg and 15 mg/ Kg body weight of rats on alternate days for a period of 7, 15 and 30 days. The accumulation of residual pesticide was maximum in brain, followed by kidney and liver and the pattern of accumulation was dose-dependant. • In vitro metabolism of fenvalerate was carried out to characterise the enzyme involved in fenvalerate metabolism in rats. Theenzyme was found to be localised mainly in outer mitochondrial membrane and microsomes in liver. This enzyme hydrolysed about 50% of fenvalerate with the formation of two degradation products which were found to be the same as were formed in vivo. The activity of the outer mitochondrial membrane localised enzyme was linear upto 30 min and to about 1.0 mg protein concentration, the pH optimum was 7.5 and K and V values were 26.32 mM and m max 0.50 mM min ' mg1 protein, respectively. The enzyme was stimulated at low EDTA concentrations (<0.5 mM), while higher concentrations of EDTA (> 0.5 mM) were found to be inhibitory causing 50% inhibition at 2 mM EDTA concentration. The enzyme required Mg2+ ions, while Mn2+ and Ca2+ were inhibitory. Presence of nonionic deter gents (Triton X-100 and Nonidet P-40) in the medium stimulated the activity of the enzyme which also catalysed further degradation of PI into a third metabolite, PHI. Fenvalerate affected various biochemical parameters in rat. There was a marked decrease in total proteins, glycogen, nucleic acids and serum cholesterol, while concen tration of major components of neutral lipids (TAG, MAG) and phospholipids (PE, PC) was increased in liver, kidney and brain. Haematological parameters showed a decline in Hb and RBC counts and an elevation in SGPT, SGOT, alkaline and acid phosphatases by 3.0-, 4.0- 1.5- and 2.0- fold, respectively. The ultrastructural changes induced by fenvalerate exposure in cells of liver and kidney of rat were investigated by transmission electron microscopy. It was found that chronic exposure to fenvalerate induced clearly noticeable changes in the ultrastructure of the rat liver cells. For example, while in unexposed rats, liver cells showed a distinct nucleus and nucleolus and a well defined endoplasmic reticulum (ER) network, the fenvalerate exposed rat liver cells showed dispersion of chromatin material, disorganisation of nucleolus, presence of crystalline rods and deposition of lipid droplets in 30 days of chronic treatIll ment with a low dose of fenvalerate (15 mg/Kg body weight). Identical ultrastructural changes were also induced in kidney cells by the fenvalerate exposure. The effect on the brain cells is likely to be identical to that of liver and kidney, although it was not investigated due to some technical difficulties. Fenvalerate also affects the subcellular membrane structure and functions. The chronic exposure of fenvalerate to rats led to an increase in the total carbohydrates and total phospholipid contents in various subcellular fractions namely, nuclear membrane, outer and inner mitochondrial membranes and plasma membrane of rat liver. There was a decrease in the protein content of treated rat liver membranes and the SDSPAGE protein profiles showed marked changes in the protein pattern and intensities of various protein bands in control and treated rats. The most prominent differences were: the 79 kDa protein was absent, the intensity of 225, 129, 127, 82, 72, 46, 44 and 15 kDa proteins was depressed, while the intensity of 220, 32, 24 and 17 kDa proteins was enhanced in nuclear membranes of exposed rat livers. Similarly, in outer mitochondrial membranes of the exposed rat liver, the 210, 180, 35 and 17 kDa proteins were absent, the relative intensity of 150, 82, 55, 48, 46, 41, 38, 31 and 27 kDa protein bands was greatly reduced, and the intensity of 162 and 18 kDa proteins was enhanced compared to control. The plasma membrane of treated rat livers showed maximum decrease in the intensity of 42 and 17 kDa bands, while 158 and 32 kDa protein bands were missing and 180, 90 and 75 kDa proteins showed increased in tensity compared to the control. The most noticeable effect was the presence of a new 35 kDa protein in the PM of the pesticide exposed rat liver cells. This 35 kDa protein may be a "stress protein" induced to counteract the effect of the pesticide. At the moment it is not clear if the 35 kDa protein is a monomeric subunit of the well known heat shock proteins, hsp 70, family.
URI: http://hdl.handle.net/123456789/567
Other Identifiers: Ph.D
Appears in Collections:DOCTORAL THESES (Bio.)

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