Effects of mercuric chloride on renal plasma membrane function after depletion or elevation of renal glutathione.

The role of renal nonprotein sulfhydryls (NPSH) in mercuric chloride-induced nephrotoxicity has been studied in various laboratories. Similarly, the importance of NPSH for mercuric ion accumulation by renal tissue also has been studied. In this study the potential role of NPSH was examined with respect to mercuric ion effects on membrane transport utilizing isolated membrane vesicles prepared from Sprague-Dawley rat kidneys. Sodium gradient-driven p-aminohippurate (PAH) transport in basolateral vesicles and glucose transport in brush border vesicles were studied. Depletion of NPSH, primarily glutathione (GSH), appeared to alter PAH but not glucose transport. HgCl2 (1 mg/kg) had no effect on either transport system in vesicles isolated from kidneys with normal GSH content, but it markedly disrupted both PAH and glucose transport in vesicles isolated from GSH-depleted rats. The most consistent effects were observed after GSH depletion with diethyl maleate plus buthionine sulfoximine. Elevation of renal GSH by administration of glutathione monoethyl ester blocked the effect of mercuric chloride (4 mg/kg) on glucose transport reported earlier. These data indicate that renal sulfhydryls not only modulate the effects of mercuric chloride, but they also may be important for normal physiological functioning of the PAH transport system.

The effects of potassium chromate and citrinin on rat renal membrane transport.

Both chromate and citrinin have been shown to produce acute renal damage. Although both substrates act on the proximal tubule in the rat, they affect different parts of that nephron segment. As with most nephrotoxicants, the mechanism(s) or subcellular target(s) for citrinin or chromate is unknown. The availability of methodology for isolation of functional membrane vesicles has afforded the opportunity to study the plasma membrane as a target for the effects of citrinin and chromate. Whether studied solely with in vitro conditions or after administration to the rat, chromate exhibited its primary action on the basolateral (BL) membrane vesicles. This was exhibited by a reduction in the p-aminohippurate (PAH) overshoot. At both 3 and 16 hr after treatment (40 mg/kg, sc) there was a significant, but relatively modest, effect on glucose transport by brush border (BB) vesicles. Citrinin, when studied in vitro, inhibited PAH transport (BL vesicles), but had only equivocal effects on BB glucose transport. However, after pretreatment of the rats with citrinin (60 mg/kg, ip), both BL and BB membrane vesicle function was reduced markedly at 3 hr. By 16 hr, an overshoot had returned for both transport substrates, although the glucose overshoot was still significantly below control. These data demonstrate that both citrinin and chromate alter proximal tubular cell membrane function and do so relatively early after administration to the rat. This effect suggests that alteration of membrane function by these nephrotoxicants is an early, if not initiating, event in the production of acute tubular necrosis.

The effects of mercuric chloride on transport by brush border and basolateral membrane vesicles isolated from rat kidney.

Both brush border and basolateral membrane vesicles were prepared from rat kidney by Percoll gradient centrifugation. The addition of mercuric chloride (100 nM) to vesicles prepared from healthy, male, Sprague-Dawley rats reduced p-aminohippurate (PAH) transport by basolateral vesicles. No effect was observed on glucose transport by brush border vesicles even at mercuric chloride concentrations as high as 10 microM. However, when the metal salt was added in the presence of 5% bovine serum albumin, basolateral PAH transport was unaffected. Transport studies also were done with vesicles isolated from rats pretreated with mercuric chloride (4 mg/kg, sc). Transport of PAH was unaffected at all times studied. Glucose transport was unaffected at 1 and 3 hr, but at 16 hr was reduced significantly. By 48 hr, brush border glucose transport had recovered. These data demonstrate that mercuric chloride can alter renal membrane function, and that the effects depend on the membrane vesicle population used. With pretreatment studies, the time after treatment also influences whether or not an effect is seen.

Entonox for casualties at 1000 m: use of nitrous oxide analgesia in Nigeria at moderate altitude.

Analgesia with nitrous oxide and oxygen (Entonox) has been found to give adequate pain relief for 90 minor casualty procedures in over 90% of cases at moderate altitude. It was self administered except in six patients. Children between 6 and 10 years of age comprised 14% of patients, and the majority of the remainder were young adults. Additional analgesia was required in 11 patients, with no increase in complications. Complications were few; drowsiness occurred in 9%, dizziness was troublesome in one patient, but there was no nausea or vomiting and no one became unconscious. In situations where trained personnel are scarce, and where supervision can only be given at the time of the procedure and even at moderate altitudes Entonox is a clinically effective safe analgesic.