Impaired renal gluconeogenesis and energy metabolism in maleic acid-induced nephropathy in rats.

Abstract

The effects of maleic acid on the gluconeogenic capacity and energy metabolism of rat kidney cortex were studied.In vitro maleic acid inhibits glucose production from various substrates by rat kidney cortex slices. Of the substrates tested, inhibition of gluconeogenesis was much greater with pyruvate, lactate andα-ketoglutarate than with glycerol, succinate, fumarate and malate. Subcutaneous injection of maleic acid produced a dose-dependent effect on aminoaciduriain vivo and on gluconeogenic capacity of slices prepared from the kidney cortices. The content of adenine nucleotides and adenylate kinase activity of kidney cortex of the maleic acid injected rats were significantly decreased. While no ultrastructural alteration of the glomeruli was demonstrable with any of the doses of maleic acid injected, electron microscopic changes of the tubules were dose-dependent, and correlated well with the degree of aminoaciduria and inhibition of gluconeogenic capacity of kidney cortex slices. Vesiculation of mitochondrial cristae found in the proximal, as well as distal convoluted tubular cells, may be associated with impairment of energy metabolism and, in turn, the reduced renal gluconeogenic capacity of the kidney cortex and the amino aciduria of maleic acid nephropathy.