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Biomedical subjects

H Mukhtar

Publications and source records attributed to H Mukhtar.

At least 271 records · Page 15Linked to original sources
PubMed1979

Biochemical effects of pure isomers of hexachlorobiphenyl: fatty livers and cell structure.

The effects of a single oral dose (50 mg/kg body wt.) of 3,4,5,3',4',5'-hexachlorobiphenyl (HCB), 2,4,5,2',4',5'-HCB or 2,3,5,2',3',5'-HCB for a period of 72 h have been studied in the male rat. Only 3,4,5,3',4',5'-HCB caused necrosis of thymocytes. 3,4,5,3',4',5'-HCB caused marked pathological changes in the liver with less marked effects being caused by 2,4,5,2',4',5'-HCB and 2,3,5,2',3',5'-HCB. Total lipid content was increased by all the isomers studied, but 3,4,5,3',4',5'-HCB had more pronounced effect on total lipid content. Lipid accumulation was pericentral in the livers obtained from rats treated with 3,4,5,3',4',5'-HCB, but midzonal in the liver obtained from the rats treated with the other two isomers. Analysis of various lipid fractions showed that triacylglycerols were increased seven-fold only by 3,4,5,3',4',5'-HCB, while phospholipids were increased slightly by 2,4,5,2',4',5'-HCB or 2,3,5,2',3',5'-HCB. Only 3,4,5,3',4',5'-HCB increased the level of total and esterified cholesterol. These results show that the fatty livers caused by 3,4,5,3',4',5'-HCB were qualitatively and quantitatively different from those caused by the other two isomers at the same dose. For the first time a hexachlorobiphenyl unchlorinated in the para position, 2,3,5,2',3',5'-HCB has been shown to be a specific inducer of cytochrome P-450. The effects of 2,3,5,2',3',5'-HCB on cell structure and phospholipid content were quantitatively similar to those caused by 2,4,5,2',4',5'-HCB. Thus, chlorination at para (4,4') positions in chlorobiphenyls is not necessarily required for biological activity. It is hypothesized that net stereoelectronic properties of the isomers or resistance to metabolism may be the underlying factor in determining structure-activity relationships.

Animals↗
PubMed1978

trans-Stilbene oxide: an inducer of rat hepatic microsomal and nuclear epoxide hydrase and mixed-function oxidase activities.

The administration of trans-stilbene oxide to rats resulted in increased hepatic microsomal and nuclear epoxide hydrase (with styrene oxide (SO), benzo[a]pyrene 4,5-oxide (4,5-BP) as substrates) and aryl hydrocarbon hydroxylase (AHH) activities. Hepatic microsomal aminopyrine N-demethylase, benzphetamine N-demethylase, and ethylmorphine N-demethylase activities were also increased. These increases in microsomal enzyme activity were dose- and time-dependent (about 100% at 200 mg/kg body weight, administered for 2 consecutive days). However, only marginal increases in hepatic microsomal NADPH-cytochrome c reductase activity and cytochrome P-450 content were observed. No apparent proliferation of hepatic endoplasmic reticulum occurred in trans-stilbene oxide pretreated rats. The administration of trans-stilbene oxide has no effect on hepatic glutathione S-transferase activities (with SO or 4,5-BPO as substrates). None of the parameters were affected in pulmonary microsomes from treated rats. The in vitro addition of trans-stilbene oxide (10(-6)--10(-2) M) did not affect hepatic epoxide hydrase or glutathione S-transferase activities.

Animals↗
PubMed1978

Epoxide metabolizing enzyme activities in rat testes: postnatal development and relative activity in interstitial and spermatogenic cell compartments.

Microsomal epoxide hydrase (EH) and 176 000 g supernatant fraction glutathione-S-transferase (GSH-S-T) activities were determined with styrene oxide as substrate in rat testes during postnatal development. The development of these enzymes was also followed in liver for comparison. Testes of 6-day-old rats had high GSH-S-T activities (66 nmol/min/mg protein), which were about 50% of the adult levels. Transferase activity then developed slowly and reached a maximum by 165 days of age. Specific testicular GSH-S-T activities of 6-day-old rats were 3--4 times those of hepatic GSH-S-T activities in the same animals. In contrast, EH activities of both liver and testes were very low in prepubertal rats, but they increased dramatically at the onset of puberty and reached maximum activities by 45 days of age. Microsomal and microsomal supernatant fractions prepared from adult rat spermatogenic cells had about twice the EH and GSH-S-T specific activities (with styrene oxide or benzo[a]pyrene 4,5-oxide as substrates) of similar fractions prepared from interstitial cells. On the other hand, benzo[a]pyrene hydroxylase (AHH) activity and cytochrome P-450 content were at least 2-fold greater in microsomes from interstitial cells than in those from spermatogenic cells.

Aging↗
PubMed1978

Effects of diethyl maleate on aryl hydrocarbon hydroxylase and on 3-methyl-cholanthrene-induced skin tumorigenesis in rats and mice.

Topical administration of diethyl maleate (DEM) and L-methionine sulfoximine (MS) reduced the L-glutathione (GSH) levels in kidneys, livers, and skin of inbred BALB/c mice. Topical administration of DEM to BALB/c mice also increased the latency period before development of skin tumors that were induced by 3-methylcholanthrene painting. Similar treatment with MS also increased the latency period, though the delay was not as striking as that observed after DEM administration. Furthermore, DEM, which was believed to be specific in its action in reducing tissue GSH, was also capable of inhibiting aryl hydrocarbon hydroxylase (AHH) both in vitro and in vivo. Cyclohexene sulfide, another "specific" inhibitor of GSH transferase, inhibited AHH activity as well. Accordingly, the blockade of AHH by DEM may have been partly responsible for the increased latency time in the skin tumorigenesis experiments.

Animals↗
PubMed1976

Mouse liver and lung glutathione s-epoxide transferase: effects of phenobarbital and 3-methylcholanthrene administration.

The effects of 3-methylcholanthrene (3MC) and phenobarbital (PB) administration on the levels of glutathione-S-epoxide transferase activity in supernatant preparations of liver and lung were studied in a number of different strains of mice, C57Bl/6, C3H, C3H-f, Balb/c-, A+ and DBA/2+. Three epoxide substrates, 3MC-11,12-oxide, styrene oxide (SO) and 3,3,3-trichloro-1,2-epoxypropane (TCPO), were employed in this investigation. PB administration (75 mg/kg body weight for 3 days) resulted in 13-57% increases in enzyme activity in the liver supernatant but was ineffective in inducing activity in lung. 3MC administration (40 mg/kg body weight for 2 days) on the other hand was without any effect on glutathione-S-epoxide transferase activity in both liver and lung.

Animals↗
PubMed1976

Glutathione-S-epoxide transferase in mouse skin and human foreskin.

Glutathione-S-epoxide transferase activity in skin was determined in six mouse strains as well as in human foreskin (from 2- to 4-day-old neonates) using two substrates, styrene oxide and 3-methylcholanthrene-11,12-oxide. Of the strains used in this study, the highest enzyme activity was noted in the skin of the Balb/c mouse. The enzyme was not inducible in skin by prior administration of 3-methylcholanthrene to the mice. Human foreskin activity was lower than that present in the adult mouse skin and ranged from 1.93 to 5.28 with styrene oxide (at 22 degrees C) and 0.17 to 0.46 nmoles/mg protein/5 min with 3-methylcholanthrene-11,12-oxide (at 37 degrees C) as substrates.

Animals↗