Abstract
Biochemical and gross pathological effects of diquat were studied with special attention to cysteine proteinase inhibitor level which was often increased in acute and chronic disorder. Diquat was fed continuously to rats at the dose of 1000 ppm in the diet. After 10 days, anorexia and severe diarrhea were observed but epistaxis and hypokinesia were not apparent. The rats were killed after feeding the diet for 13.5 days and plasma components such as acute phase reactant proteins and some vitamins which act as antioxidants were examined. The results showed that α-cysteine proteinase inhibitor (α-CPI) increased to 9-fold and vitamin C radical increased to 1.6-fold, whereas α1 proteinase inhibitor (α1-PI) decreased to 0.9-fold and vitamins C and E were the same as the control. Among three components of α-CPI, the T kininogen level in intoxicated rat plasma was about 20-fold, whereas the high molecular weight kininogen level was about 2-fold of the control. Diquat also enhanced the cysteine proteinase inhibitor (CPI) level to 20-fold in kidney and to 7- to 10-fold in the other organs. The large increment of T kininogen in these organs was also confirmed immunologically. The kidney showed a granular degeneration and its weight increased to 1.2-fold of control. The other organs showed neither gross pathological alteration nor weight change, compared with the control. The diquat distribution was highest in spleen and next highest in kidney among several organs. These results were compared with those caused by paraquat.
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Baldwin RC, Pasi A, MacGregor JT, Hine CH (1975) The rates of radical formation from the dipyridylium herbicides paraquat. diquat, and morfamquat in homogenates of rat lung, kidney, and liver: an inhibitor effect of carbon monoxide. Toxicol Appl Pharmacol 32: 298–304
Bus JS, Gibson JE (1984) Paraquat: model for oxidant-initiated toxicity. Environ Health Perspec 55: 37–46
Clark DG, Hurst EW (1970) The toxicity of diquat. Br J Ind Med 27: 51–55
Cotgreave IA, Sandy MS, Berggren M, Moldeus PW, Smith MT (1987) N-Acetylcysteine and glutathione-dependent protective effect of PZ51 (Ebselen) against diquat-induced cytotoxicity in isolated hepatocytes. Biochem Pharmacol 36: 2899–2904
Harada N, Saito S, Minakata K (1991) Effects of vitamin E on toxicity by minute amounts of paraquat fed continuously to rats. J Nutr Sci Vitaminol 37: 1–13
Hayashi I, Oh-ishi S, Enjyoji K, Kato H, Iwanaga S (1986) A radio-immunoassay for rat T-kininogen as an acute phase rectant. Chem Pharm Bull 34: 3502–3505
Litchfield MH, Daniel JW, Longshaw S (1973) The tissue distribution of the bipyridylium herbicides diquat and paraquat in rats and mice. Toxicology 1: 155–165
Minakata K, Asano M, Takahashi Y, Harada N (1984) Increase of α-cysteine proteinase inhibitor level in serum of vitamin E deficient muscular dystrophic rats. Nutr Rep Int 29: 445–459
Minakata K, Asano M, Takahashi Y, Harada N (1987) Enhancement of testicular cysteine proteinase inhibitor levels in vitamin E deficient rats. J Nutr 117: 1416–1421
Minakata K, Suzuki O, Saito S, Harada N (1993) Ascorbate radical levels in human sera and rat plasma intoxicated with paraquat and diquat. Arch Toxicol 67: 126–130
Minakata K, Suzuki O, Oh-ishi S, Hayashi I, Saito S, Harada N (1995) Acute-phase reactant proteins and antioxidants in rats intoxicated chronically with paraquat. J Toxicol Environ Health 44: 29–41
Nakagawa Y, Cotgreave IA, Moldeus P (1991) Relationships between ascorbic acid and α-tocopherol during diquat-induced redox cycling in isolated rat hepatocytes. Biochem Pharmacol 42: 883–888
Oh-ishi S, Hayashi I, Kusunoki A, Nagashima Y, Hayashi M, Yamaki K, Utsunomiya I, Yamasu A (1988) Developmental and sexual differences of T-kininogen levels in rat plasma and liver. Biochem Biophys Res Commun 150: 1069–1076
Okamoto H, Greenbaum LM (1983) Isolation and structure of T-kinin. Biochem Biophys Res Commun 112: 701–708
Sandy MS, Moldeus P, Ross D, Smith MT (1986) Role of redox cycling and lipid peroxidation in bipyridyl herbicide cytotoxicity. Biochem Pharmacol 35: 3095–3101
Sandy MS, Monte DD, Smith MT (1988) Relationships between intracellular vitamin E, lipid peroxidation, and chemical toxicity in hepatocytes. Toxicol Appl Pharmacol 93: 288–297
Snedecor GW, Cochran WG (1967) Statistical methods. 6th edn. Iowa State University Press, Ames, Iowa. Chapter 4
Tomita M (1991) Comparison of one-electron reduction activity against the bipyridylium herbicides, paraquat and diquat, in microsomal and mitochondrial fractions of liver, lung and kidney (in vitro). Biochem Pharmacol 42: 303–309
Urban J, Chan D, Schreiber G (1979) A rat serum glycoprotein whose synthesis rate increases greatly during inflammation. J Biol Chem 254: 10565–10568
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Minakata, K., Suzuki, O., Oh-ishi, S. et al. Diquat increases cysteine proteinase inhibitors greatly in rat plasma and tissues. Arch Toxicol 69, 318–321 (1995). https://doi.org/10.1007/s002040050177
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DOI: https://doi.org/10.1007/s002040050177