Effect of oral exposure to fenitrothion and 3-methyl-4-nitrophenol on splenic cell populations and histopathological alterations in spleen in Wistar rats

Abstract

Fenitrothion (FNT) is used throughout the world as an insecticide in agriculture. To investigate the effect of FNT on the splenocytes and the underlying mechanism, FNT and its main metabolite, 3-methyl-4-nitrophenol (MNP), were administered orally to Wistar rats in daily doses of 0, 5 and 10 mg/kg, 4-5 days/week for 9 weeks. Splenocytes were harvested from control and exposed rats, and the following cell phenotypes were quantified by flow cytometry: (1) B cells (PE-CD45RA), (2) T cells (FITC-CD3), (3) T cell subsets (PE-CD4 and PerCPCD8), (4) natural killer (NK) cells (FITC-CD161a), (5) macrophages (FITC-CD11b), and (6) granulocyte (PE-granulocyte). Body weight, weight of the spleen, and histopathological alterations of spleens were also examined. The percentage of splenic CD8+ T cells and the ratio of CD8/CD4 in the group receiving 10 mg/kg FNT, and the percentages of splenic CD3+ and CD8+ T cells in the group receiving 10 mg/kg MNP were significantly decreased compared with those in the controls. FNT exposure also significantly decreased the weight of the spleen and body weight. In addition, apoptotic lymphocytes in spleen were observed in FNT-exposed rats under transmission electron microscope. However, FNT and MNP exposures did not affect splenic NK cells, B cells, macrophages, and granulocytes. The above findings indicate that FNT and MNP may selectively affect splenic T cells in rats.

Keywords

B cells fenitrothion (FNT)histopathological alterations 3-methyl-4-nitrophenol (MNP)NK splenocytes T cells

References

Richardson ML F9: Fenitrothion. In: Richardson ML (ed.) The dictionary of substances and their effects. Vol 2. Cambridge: The Royal Society of Chemistry, 1993, p.491-497.

Brzeziński J. , Wysocka-Paruszewska B. Neurochemical alterations in rat brain as a test for studying the neurotoxicity of organophosphorus insecticides. Arch Toxicol Suppl 1980; 4: 475-478.

Durham HD , Ecobichon DJ An assessment of the neurotoxic potential of fenitrothion in the hen . Toxicology 1986; 41: 319-332.

Sohoni P. , Lefevre PA , Ashby J. , and Sumpter JP Possible androgenic/anti-androgenic activity of the insecticide fenitrothion . J Appl Toxicol 2001; 21: 173-178.

Okahashi N. , Sano M. , Miyata K. , Tamano S. , Higuchi H. , Kamita Y. , et al. Lack of evidence for endocrine disrupting effects in rats exposed to fenitrothion in utero and from weaning to maturation. Toxicology 2005; 206: 17-31.

Turner KJ , Barlow NJ , Struve MF , Wallace DG , Gaido KW , Dorman DC , et al. Effects of in utero exposure to the organophosphate insecticide fenitrothion on androgen-dependent reproductive development in the Crl:CD(SD)BR rat. Toxicol Sci 2002; 68: 174-183.

Struve MF , Turner KJ , and Dorman DC Preliminary investigation of changes in the sexually dimorphic nucleus of the rat medial preoptic area following prenatal exposure to fenitrothion . J Appl Toxicol 2007; 27: 631-636.

Moon CK , Yun YP , Lee SH , and Lee YS Effects of some organophosphate pesticides on the murine immune system following subchronic exposure (I). Arch Pharm Res 1986 ; 9: 175-181.

Moon CK , Yun YP , and Lee SH Effects of some organophosphate pesticides on the murine immune system following subchronic exposure (II). Arch Pharm Res 1986 ; 9: 183-187.

10.

Nakashima K. , Yoshimura T. , Mori H. , Kawaguchi M. , Adachi S. , Nakao T. , et al. Effects of pesticides on cytokines production by human peripheral blood mononuclear cells-fenitrothion and glyphosate (Article in Japanese). Chudoku Kenkyu 2002 ; 15: 159-165.

11.

Kunimatsu T. , Kamita Y. , Isobe N. , and Kawasaki H. Immunotoxicological insignificance of fenitrothion in mice and rats. Fundam Appl Toxicol 1996 ; 33: 246-253.

12.

Warren M. , Spencer HC , Churchill FC , Francois VJ , Hippolyte R. , and Staiger MA Assessment of exposure to organophosphate insecticides during spraying in Haiti: monitoring of urinary metabolites and blood cholinesterase levels . Bull World Health Organ 1985; 63: 353-360.

13.

Meaklim J. , Yang J. , Drummer OH , Killalea S. , Staikos V. , Horomidis S. , et al. Fenitrothion: toxicokinetics and toxicologic evaluation in human volunteers. Environ Health Perspect 2003; 111: 305-308.

14.

Li C. , Takahashi S. , Taneda S. , Furuta C. , Watanabe G. , Suzuki AK , et al. Impairment of testicular function in adult male Japanese quail (Coturnix japonica) after a single administration of 3-methyl-4-nitrophenol in diesel exhaust particles. J Endocrinol 2006; 189: 555-564.

15.

Li C. , Taneda S. , Suzuki AK , Furuta C. , Watanabe G. , and Taya K. Effects of 3-methyl-4-nitrophenol in diesel exhaust particles on the regulation of testicular function in immature male rats. J Androl 2007; 28: 252-258.

16.

Hayes WJ Jr , and Laws ER Jr. Fenitrothion. In: Hayes WJ (ed.) Handbook of pesticide toxicology. Classes of pesticides Vol 2. San Diego, CA: Academic Press, 1991 , p.1020-1023.

17.

Li Q. , Minami M. , Hanaoka T. , and Yamamura Y. Acute immunotoxicity of p-chloronitrobenzene in mice: II. Effect of p-chloronitrobenzene on the immunophenotype of murine splenocytes determined by flow cytometry . Toxicology 1999; 137: 35-45.

18.

Li Q. , Hirata Y. , Piao S. , and Minami M. Immunotoxicity of N,N-diethylaniline in mice: effect on natural killer activity, cytotoxic T lymphocyte activity, lymphocyte proliferation response and cellular components of the spleen. Toxicology 2000; 150: 179-189.

19.

Fujimoto K. , Matsui M. , Fujii T. , and Kawashima K. Decreased acetylcholine content and choline acetyl-transferase mRNA expression in circulating mononuclear leukocytes and lymphoid organs of the spontaneously hypertensive rat. Life Sci 2001; 69: 1629-1638.

20.

Talcott PA , Exon JH , and Koller LD The effects of methylnitrosourea (MNU) on natural killer (NK) cell cytotoxicity and cytokine production in rats. Carcinogenesis 1990; 11: 829-834.

21.

WHO. Fenitrothion. In: WHO (ed.) Environmental health criteria, 133. Geneva : World Health Organization, 1992 . p.75-81.