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Everted sacs of distinct segments of small intestine from male and female rats were incubated with 2 microM of aluminum (Al). In duodenum, Al significantly diminished calcium flux (JCams) in cycling females (31%, P < 0.01) and in males (17%, P < 0.05). Incubation under anaerobic conditions nullified the inhibition of Al on JCams both in male and in female duodenal sacs. Jejunal and ileal JCams measured under aerobic conditions were not modified by the presence of Al in mucosal fluid compared to Al-free controls, neither in males nor in cycling females. In ovariectomized female rats treated with estrogen the studies of dose-response curves showed that the sensitivity to the effect of Al on JCams was raised (the dose that produced half maximum response diminished) with increasing 17 beta-estradiol serum levels, without changes in the maximum response. In castrated male rats injected with testosterone, the effect of Al on duodenal JCams was found to be independent of testosterone levels. In summary, our results demonstrated that the Al inhibition on duodenal JCams was influenced by sexual hormone levels in females but was independent of them in males.

The intravenous administration of insulin plus glucose in anesthetized rats caused, within 30 min, an increase of about 56% in hepatic cytosolic glutathione S-transferase (GST) activity, but it did not affect the microsomal enzyme. The injection of glucagon resulted, at the same time, in a 43% drop in the hepatic cytosolic GST, without affecting the microsomal GST. The insulin-dependent increase in cytosolic GST activity was abolished by the pretreatment of the animals with an inhibitor of protein synthesis (cycloheximide). A kinetic analysis revealed a non-competitive inhibition caused by glucagon upon the cytosolic enzyme. In addition, the presence of insulin did not interfere with the effectiveness of glucagon, and vice versa. We propose that: (1) the effect of insulin on hepatic cytosolic GST activity requires protein synthesis; (2) glucagon produces an inhibition of hepatic cytosolic GST, which could be mediated by cytosolic effectors such as adenosine 3'-5'-cyclic monophosphate (cAMP); (3) the effects of glucagon and insulin were not mutually exclusive; (4) hepatic microsomal GST is regulated by different mechanism(s).

The effect of aflatoxin B1 (AFB1) on the glutathione S-transferase activity (GST) and on non-protein thiol levels of different tissues was studied in adult male Wistar rats. Animals received a single dose of the toxin (100 or 500 micrograms/kg body wt., p.o.), and were studied 6 or 24 h after administration. GST was determined in liver, renal cortex, duodenum, jejunum-ileum and distal ileum, using 3 substrates: 1-chloro-2,4-dinitrobenzene (CDNB), trans-4-phenyl-3-buten-2-one (PBO) and 1,2-epoxyethylbenzene (STOX). The non-protein thiol content of all tissues tested increased with the lowest dose at 6 h, returning to normal values at 24 h, while the higher dose produced a significant decrease in reduced thiol levels at 6 h, returning to normal values at 24 h. AFB1 administration induced, independently of dose and tissue, total GST (CDNB) and epoxide-transferase activity (STOX) while A--C-type transferases (PBO) were inhibited. Almost all activities returned to normal values at 24 h. In cases of enzyme induction there was in general an increase in Vmax and a decrease in apparent Km. The opposite was seen in cases of inhibition. In conclusion, the results provide evidence that extrahepatic GST could be important in the overall process of detoxification of AFB1. The behavior seen in hepatic and extrahepatic tissues revealed the functions of catalysis (B-type transferases) and covalent bond formation, as well as inactivation by probable AFB1 metabolites (A--C-type transferases).

The effect of streptozotocin (SZ) administration on sodium [14C]taurocholate (TC) transmural transfer was studied in the everted rat ileum. The excretion of fecal bile acids was also studied in living rats injected with that compound. The viability of the preparation used for the in vitro experiments was evaluated by light microscopy and by the rate of glucose uptake by tissue from the mucosal fluid. The results obtained showed that TC transfer to the serosal fluid was impaired after 24 h of SZ injection, as well as the active transport observed in control preparations. The amount of TC accumulated in the intestinal tissue was also diminished. In addition, total ATPase activity of tissue was decreased, and intracellular electrolyte concentration was altered. Therefore, a slower saturation of binding sites could be responsible for the effects of SZ on TC tissue accumulation, and a decreased ATPase activity for the impairment of the TC concentrative transport system. The results observed in vitro were supported by data in vivo because fecal bile acid excretion was significantly diminished in SZ-treated rats.

The effect of streptozotocin (SZ) on bile flow (BF) and on protein and lipid biliary outputs were studied in rats with bile fistula. SZ was given i.v. as a single dose (50 mg/kg body wt.). Nicotinamide was administrated (500 mg/kg body wt., i.p.) 10 min prior to SZ. Decreases in BF and in biliary outputs of bile acids, proteins and acid phosphatase were observed in SZ-treated rats; conversely, the biliary excretion of cholesterol and phospholipids was increased. Nicotinamide pretreatment prevented the hyperglycemia induced by SZ and also suppressed the SZ-mediated increase of cholesterol and phospholipid biliary outputs, suggesting that they could be related to the diabetic state. The results also demonstrated a direct effect of SZ on BF and on the biliary excretion of bile acids and proteins. Since SZ is used clinically, and in experimental diabetes, the effects produced by this drug on the rat liver should be considered.