A study of gender, strain and age differences in mouse liver glutathione-S-transferase

doi:10.1016/0742-8413(94)00079-P

Comparative Biochemistry and Physiology Part C: Pharmacology, Toxicology and Endocrinology

Volume 110, Issue 1, January 1995, Pages 35-40

https://doi.org/10.1016/0742-8413(94)00079-P Get rights and content

Abstract

The hepatic cytosolic glutathione S-transferase (GST) activity in four strains of the mouse and one strain of the rat was studied with the substrates 1-chloro-2,4-dinitrobenzene (CDNB), 1,2-dichloro-4-nitrobenzene (DCNB), ethachrynic acid (ETHA), cumene hydroperoxide (CU) and atrazine as the in vitro substrates. In the mouse, significant gender, strain and age-related differences in the GST activity towards CDNB and atrazine were found between adolescent and sexually mature males and females of the CD-1, C57BL/6, DBA/2 and Swiss-Webster strains, and the differences were larger with atrazine as the substrate. With DCNB and CU a similar tendency was observed, however not significant for all strains. The GST activity towards ETHA was also gender and strain specific, but revealed no age-related differences. The herbicide atrazine seems to be a useful substrate in the study of strain and age-related differences in the mouse GST class Pi.

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Echinodorus macrophyllus (Kunth.) Micheli (Alismataceae), known as chapéu-de-couro in Brazil, is popularly used to treat inflammatory diseases. We have previously demonstrated a significant reduction in the acute inflammation for the aqueous extract of E. macrophyllus (AEEm) and its ethanolic fraction (Fr20) and described that hydroxycinnamoyl derivatives present in SF1 (Fr20 subfraction) showed higher anti-inflammatory properties by mechanisms that include a reduction of TNF-α, IL-1β, CKCL1/KC, LTB4, and PGE2 levels in exudate.
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Fr20 was earlier fractionated on the Sephadex LH-20 column, yielding mainly four subfractions, including SF1. The SF1 toxicity was evaluated in mice challenged with carrageenan on the air pouch inflammation model and orally treated for five days. The body weight was monitored daily, and the organs were weighed after the euthanasia. Hematological and biochemical determinations were carried out using specific commercial kits and following the protocols provided by the manufacturers. The organs were fixed, sectioned, processed for hematoxylin and eosin staining, and analyzed by light microscopy. Genotoxicity assessment was performed by the alkaline single-cell gel electrophoresis. Livers were processed for ethoxyresorufin-O-deethylase (EROD) and Glutathione S-transferase (GST) assays.
SF1 exhibited low toxicity, as no significant discrepancy was observed in the relative weight of the body organs of mice. Moreover, the daily treatment with SF1 did not alter the number and percentage of red blood cells or hemoglobin concentration in the blood. The treatment with SF1 did not affect the creatinine concentration, but the 25 mg/kg dose reduced the plasma urea level and uric acid, suggesting its use in treating acute renal failure. The parameters analyzed did not present biochemical alterations indicative of liver disease. Regarding serum triglyceride and cholesterol levels, a significant decrease was detected in both parameters in mice treated with SF1. In addition, the histopathological analysis showed that inflammatory focus in the livers seemed more relevant in the control groups than in those treated. There were no significant changes in the renal or splenic tissues of animals treated with SF1. Treatment with SF1 also does not have a genotoxic effect on liver cells.
Treatment with SF1 showed no toxicity in mice at doses equivalent to those recommended for humans, which provides evidence of the safety of the therapeutic use of this subfraction.
Protective effect of aqueous extract of Phyllanthus fraternus against bromobenzene induced changes on cytosolic glutathione S-transferase isozymes in rat liver
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Citation Excerpt :
Cytosolic GSTs comprise a large family of detoxification enzymes that function as hetero or homodimers and are classified into seven classes termed as alpha (α), mu (µ), theta (θ), pi (π), zeta (ζ), chi (χ) and sigma (σ) [4–6]. The most abundant classes expressed in mammalian tissues are Alpha (GSTA), Mu (GSTM) and Pi (GSTP) [7,8]. The pattern of expression of these isozymes are specific for species, age and organs [9].
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In vitro and in vivo toxicological evaluation of extract and fractions from Baccharis trimera with anti-inflammatory activity
2011, Journal of Ethnopharmacology
Citation Excerpt :
The activity towards ETHA was determined with 500 mg of protein, 0.25 mM GSH and 0.2 mM ETHA. Every assay was carried out in triplicate with correction for non-enzymatic conjugation (Egaas et al., 1995). Protein concentration was determined according to Peterson (1977) using bovine serum albumin as standard (10–100 μg).
Baccharis trimera (Less) DC. (Asteraceae), popularly known in Brazil as “carqueja”, have been used in folk medicine to treat gastrointestinal, hepatic and renal diseases, and inflammatory processes as rheumatism.
To evaluate the in vitro and in vivo toxicological effects of anti-inflammatory Baccharis trimera aqueous extract and fractions.
Aqueous extract of Baccharis trimera (AEBt) was produced by infusion in boiling water. After lyophylization AEBt was extracted with 80% ethanol, originating the ethanolic supernatant fraction (EFBt) and the aqueous sediment fraction (AFBt). Anti-inflammatory properties of AEBt, EFBt or AFBt (3, 30 or 300 μg/kg b.w.) were evaluated by the carrageenan-induced mouse paw edema using indomethacin (10 mg/kg) as positive control. The growth of rat hepatoma cells (HTC) and human embryo kidney epithelial cells (HEK) was determined by protein staining assay. Cytotoxicity was assayed by the tetrazolium salt (MTT) reduction. Cyclosporin was used as reference cytotoxic drug for spleen cells and doxorubicin for HTC and HEK cells. For in vivo toxicological evaluation SW male mice were daily and oral (gavage) treated with extract/fractions at 4.2 mg/kg or 42 mg/kg during 15 days. After treatment liver or kidney cells were submitted to comet assay to determine the DNA damage index, and the glutathione S-transferase activity was assayed towards ETHA (class Pi) and CDNB (several classes). Mutagenicity was evaluated by the Ames test using Salmonella typhimurium strains TA97, TA98, TA100, and TA102.
The anti-inflammatory effects of EFBt were higher than those of AEBt or AFBt. Mice treatment (3–300 μg/kg) with AFBt reduced the paw edema (3 h) at lower levels (29.2–37.3%; P < 0.01), than those observed for AEBt (44.7–54.2%; P < 0.001), EFBt (49.3–58.2%; P < 0.001) or indomethacin (64.6%, P < 0.001, 10 mg/kg). The growth of kidney cells (HEK) was inhibited by AEBt (IC₅₀ 182.6 μg/ml), EFBt (IC₅₀ 78.1 μg/ml) and AFBt (IC₅₀ 86.2 μg/ml), with lower effects on HTC hepatic cell (IC₅₀ 308.8 μg/ml, 396.5 μg/ml and 167.9 μg/ml, respectively). As evaluated by MTT test, AFBt exhibited cytotoxicity for HEK cells (IC₅₀ 372.5 μg/ml), but none for HTC ones; by the way, AFBt stimulated spleen cells (EC₅₀ 2.2 μg/ml) while cyclosporine, a cytotoxic reference drug inhibited them with IC₅₀ of 0.42 μg/ml; the IC₅₀ for doxorubicin for HEK and HTC cells was 0.28 μg/ml and 14.4 μg/ml, respectively, at 96 h. No mutagenic potential was observed. Mice treatment with AEBt or AFBt at 42 mg/kg for 15 days altered the kidney relative weight, but not at 4.2 mg/kg. Baccharis trimera did not change liver, spleen or popliteal lymph node relative weight. DNA damage index of kidney cells was observed on mice treated with AEBt/AFBt, but not on animals treated with EFBt, while DNA lesions were detected on liver cells only after AFBt treatment. The general activities of hepatic GST and Pi GST were reduced by EFBt and AFBt treatment, respectively.
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Age composition and age-related trends of antioxidant enzyme activities superoxide dismutase (SOD), catalase (CAT), peroxidase (PER), glutathione reductase (GR) and glutathione-S-transferase (GST) in the blood of seven Black Sea teleosts (Carangidae, Centracanthidae, Gadidae, Mullidae, Gobiidae and Scorpaenidae) collected in marine coastal area of Sevastopol (Ukraine) were studied. In the catches the animals of 1 – 2 years of age dominated while in the Scorpaena porcus population the number of relatively elder individuals belonging to classes of 3–4 years was the highest. The trends of antioxidant enzyme activities in blood were not uniform. Three types of age-dependent responses were indicated in fish blood: 1. enzymatic activity did not change with age; 2. enzymatic activity decreased with age and 3. enzyme activity increased with age or varied unclearly. The interspecies differences of age-related enzymatic activities associated with the specificity of fish biology and ecology were indicated. Despite no clear evidence of age-related differences between fish species belonging to different ecological groups both benthic forms exhibited similar age-dependent trends of SOD and PER. The correlations between blood antioxidant enzyme activities in fish belonging to suprabenthic and benthic/pelagic groups demonstrated the intermediate values as compared to the benthic and pelagic forms. The results suggest the importance of age trends for biomarkers in fish monitoring studies.
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This chapter is devoted to understanding the differential sensitivity of the nervous system based on the developmental stage of exposure. Age-related differences in sensitivity to pesticides can be attributed to both toxicokinetic and toxicodynamic principles. It is clear from review of both experimental and clinical data that there is no hard-and-fast rule regarding age-related differences in sensitivity to pesticides. While neonates may be more sensitive to the acute toxicity of some pesticides, adults may be more sensitive to others. Even when a single pesticide is considered, age-related differences in sensitivity may change qualitatively depending on the conditions of exposure or the endpoint measured. While maturational differences in biotransformation capacity may be limiting in some cases, e.g., with acute, high-level exposures where detoxification enzymes could become saturated, such metabolic differences may be of lesser importance with repeated, lower levels of exposure to the same pesticides. Similarly, differences in the ability to recover following pesticide exposure may be much more important when repeated exposures occur than following acute exposures. Relative sensitivity can be expressed in one of two ways, i.e., a subpopulation exhibits differences in sensitivity to a particular form of toxicity or a subpopulation exhibits qualitatively different forms of toxicity to the same pesticide. Risk assessments are typically performed using a “critical” endpoint, generally the most sensitive endpoint to the toxicant in question derived from a series of toxicity studies.
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This chapter is devoted to understanding the differential sensitivity of the nervous system based on the developmental stage of exposure. Age-related differences in sensitivity to pesticides can be attributed to both toxicokinetic and toxicodynamic principles. It is clear from review of both experimental and clinical data that there is no hard-and-fast rule regarding age-related differences in sensitivity to pesticides. While neonates may be more sensitive to the acute toxicity of some pesticides, adults may be more sensitive to others. Even when a single pesticide is considered, age-related differences in sensitivity may change qualitatively depending on the conditions of exposure or the endpoint measured. While maturational differences in biotransformation capacity may be limiting in some cases, e.g., with acute, high-level exposures where detoxification enzymes could become saturated, such metabolic differences may be of lesser importance with repeated, lower levels of exposure to the same pesticides. Similarly, differences in the ability to recover following pesticide exposure may be much more important when repeated exposures occur than following acute exposures. Relative sensitivity can be expressed in one of two ways, i.e., a subpopulation exhibits differences in sensitivity to a particular form of toxicity or a subpopulation exhibits qualitatively different forms of toxicity to the same pesticide. Risk assessments are typically performed using a “critical” endpoint, generally the most sensitive endpoint to the toxicant in question derived from a series of toxicity studies.

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A study of gender, strain and age differences in mouse liver glutathione-S-transferase

Abstract

Analyt. Biochem.

Comp. Biochem. Physiol.

Comp. Biochem. Physiol.

Pest. biochem. Physiol.

J. biol. Chem.

Biochem. biophys. Res. Commun.

Biochem. biophys. Res. Commun.

Int. J. Biochem.

Analyt. Biochem.

Comp. Biochem. Physiol.

Mouse strain differences in glutathione S-transferase activity and aflatoxin B1 biotransformation

Toxic. Lett.

Mouse strain differences in glutathione S-transferase activity and aflatoxin B₁ biotransformation