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Aminoglycosides (AG) such as gentamicin are antimicrobial drugs widely used in the hospital setting due to their efficacy in the treatment of severe gram-negative bacterial infections. However, all AG have the potential to cause nephrotoxicity. Two studies have been conducted (1) to assess the protein level of a diet that would give the best renal outcome with gentamicin administration, and (2) to get a better idea about the rhythms of food ingestion associated with the different protein levels. Adult female Sprague–Dawley rats fully adapted to a standard chow diet, the standard chow with 20% or 55% added casein were chronically treated for 10 days with a nephrotoxic dose of gentamicin sulfate (40 mg/kg/day, i.p.) or a saline solution. Food ingestion patterns of rats were recorded every hour using a Diet Scan system and gentamicin nephrotoxicity indices were measured. The second study used rats that were fed the same diets and given a sham injection. Corticosterone was assayed to quantify the stress of the animals. Results showed that chronic gentamicin treatment leads to a decrease in food intake and flattening of the rhythms of food ingestion. Also, chow feeding and the 20% casein diet were found to be more protective against gentamicin-induced nephrotoxicity than the 55% casein diet. Therefore, while a protein-rich diet can be protective against gentamicin-induced nephrotoxicity, the present study demonstrates that a diet too high in protein might rather be harmful to the kidneys.

This grant funded in part the Fourth International Conference on Biological Rhythms and Medications held in Nice, France 12-15 March 1990, sponsored by the International Society for Chronobiology. The published Proceedings compiled in this final report deal with seven major themes: (1) neurobiology, (2) endocrinology and gastroenterology, (3) cardiovascular agents, (4) metabolic aspects, (5) immunology and cancer, (6) general chronopharmacology and (7) chronotherapeutics.