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Nephrotoxicity of butylated hydroxytoluene in phenobarbital-pretreated male rats

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Abstract

A single large dose of butylated hydroxytoluene (BHT, 1000 mg/kg) in male Fischer 344 rats produced some renal damage, reduced accumulation of p-aminohippuric acid in renal slices, proteinuria and enzymuria, in addition to hepatic damage. Further, prior administration of phenobarbital (80 mg/kg, i. p., daily for 4 days) in the high-dose BHT-treated male rats produced renal damage accompanied by slight tubular necrosis. The renal damage was confirmed by biochemical and histological changes. These changes were dose dependent, with a maximum at 24 h after BHT administration, but had returned to the normal range by 48 h. Female rats, on the other hand, were less susceptible to BHT-induced renal and hepatic damage than male rats. The results indicate sex differences in BHT-induced renal or hepatic damage.

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References

  • Bradford M (1976) A rapid and sensitive method form the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 72: 248–254

    Google Scholar 

  • Cross RJ, Taggart VJ (1950) Renal tubular transport: Accumulation of p-aminohippurate by rabbit kidney slices. Am J Physiol 161: 181–190

    Google Scholar 

  • Daniel JW, Gage JC (1965) The absorption and excretion of butylated hydroxytoluene (BHT) in the rat. Food Cosmet Toxicol 3: 405–415

    Google Scholar 

  • Daniel JW, Gage JC, Jones DI (1968) The metabolism of 3,5-ditert-butyl-4-hydroxytoluene in the rat and in the man. Biochem J 106: 783–790

    Google Scholar 

  • Fawcett JK, Scott JE (1960) A rapid and precise method for the determination of urea. J Clin Pathol 13: 156–159

    Google Scholar 

  • Ford SM, Hook JB, Bond JT (1980) The effects of butylated hydroxyanisole and butylated hydroxytoluene on renal function in the rat. II Effects on organic acid and base transport. Food Cosmet Toxicol 18: 21–26

    Google Scholar 

  • Gram TE, Okine LK, Gram RA (1986) The metabolism of xenobiotics by certain extrahepatic organs and its relation to toxicity. In: George R, Okun R, Cho AK (eds) Ann Rev Pharmacol Toxicol 26. Annual Reviews Inc, California, pp 259–291

    Google Scholar 

  • Horak E, Hopfer SM, Sunderman FW (1981) Spectrophotometric assay for urinary N-acetyl-β-d-glucosaminidase activity. Clin Chem 27: 1180–1185

    Google Scholar 

  • Karmen A (1955) A note on the spectrophotometric assay of glutamic-oxalacetic transaminase in human blood serum. J Clin Invest 34: 131–133

    Google Scholar 

  • Karplyuk IA (1960) Elementary raw fats containing phenolic antioxidants. An elevation from the point of view of hygiene. Vopr Pitaniya 19: 67

    Google Scholar 

  • Kind PPN, King EJ (1954) Estimation plasma phosphatase by determination of hydrolyzed phenol with aminoantipyrine. J Clin Path 7: 322–326

    Google Scholar 

  • Ladomery LG, Ryan AJ, Wright SE (1967) The excretion of (14C) butylated hydroxytoluene in the rat. J Pharm Pharmacol 19: 383–387

    Google Scholar 

  • Meyer O, Blom L, Olsen P (1978) Influence of diet and strain of rat on kidney damage observed in toxicity studies. Arch Toxicol suppl 1: 355–358

    Google Scholar 

  • Mizutani T, Nomura H, Nakanishi K, Fujita S (1987) Hepatotoxicity of butylated hydroxytoluene and its analogs in mice depleted of hepatic glutathione. Toxicol Appl Pharmacol 87: 166–176

    Google Scholar 

  • Nakagawa Y, Hiraga K, Suga T (1979a) Biological fate of butylated hydroxytoluene (BHT); binding in vivo of BHT to macromolecules of rat liver. Chem Pharm Bull 27: 442–446

    Google Scholar 

  • Nakagawa Y, Hiraga K, Suga T (1979b) Biological fate of butylated hydroxytoluene (BHT); binding in vitro of BHT to liver microsomes. Chem Pharm Bull 27: 480–485

    Google Scholar 

  • Nakagawa Y, Hiraga K, Suga T (1981) Biological fate of butylated hydroxytoluene (BHT); binding of BHT metabolites to cysteine in vitro. Biochem Pharmacol 30: 887–890

    Google Scholar 

  • Nakagawa Y, Hiraga K, Suga T (1983) On the mechanism of covalent binding of butylated hydroxytoluene to microsomal protein. Biochem Pharmacol 32: 1417–1421

    Google Scholar 

  • Nakagawa Y, Tayama K, Nakao T, Hiraga K (1984) On the mechanism of butylated hydroxytoluene-induced hepatic toxicity in rats. Biochem Pharmacol 33: 2669–2674

    Google Scholar 

  • Nakagawa Y, Tayama K, Nakao T, Hiraga T (1985) Effect of cobaltous chloride on butylated hydroxytoluene-induced hepatic necrosis in rats. Toxicol Lett 24: 85–89

    Google Scholar 

  • Newton JF, Kuo CH, Gembory NW, Mudge GH, Hook JB (1982) Nephrotoxicity of p-aminophenol, a metabolite of acetaminophen, in the Fischer 344 rat. Toxicol Appl Pharmacol 65: 336–344

    Google Scholar 

  • Ohnhaus EE (1972) Urinary excretion of chlorothiazide in rats before and after phenobarbitone administration. Experientia 28: 821–822

    Google Scholar 

  • Ohnhaus EE, Siegl H (1974) Changes in renal function following chronic phenobarbitone administration. Br J Pharmacol 52: 141

    Google Scholar 

  • Powell CJ, Connelly JC, Jones SM, Grasso P, Bridges JW (1986) Hepatic responses to the administration of high doses of BHT to the rat: their relevance to hepatocarcinogenicity. Food Chem Toxicol 24: 1131–1143

    Google Scholar 

  • Smith HW, Finkelstein N, Aliminosa L, Crawford B, Graber M (1945) The renal clearance of substituted hippuric acid derivatives and other aromatic acids in dog and man. J Clin Invest 25: 388–404

    Google Scholar 

  • WHO Technical Report Series (1987) Evaluation of certain food additives and contaminants. Thirtieth Report of the Joint FAD/WHO Expert Committee on Food Additives, Geneva, pp 12–52

  • Wroblewski F, LaDue JS (1955) Lactic dehydrogenase activity in blood. Proc Soc Exp Biol Med 90: 210–213

    Google Scholar 

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Nakagawa, Y., Tayama, K. Nephrotoxicity of butylated hydroxytoluene in phenobarbital-pretreated male rats. Arch Toxicol 61, 359–365 (1988). https://doi.org/10.1007/BF00334616

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  • DOI: https://doi.org/10.1007/BF00334616

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