Animal renal targeting

Target Organ Toxicity. This section focuses on mechanisms for sensitive health effects of major concern for lead—cardiovascular effects, hematological effects, and neurological effects, particularly in children. Bone is a major sink for lead, and there is some limited information regarding the effects of lead on bone and potential mechanisms of action. Renal effects occur at relatively high blood lead levels and evidence of renal carcinogenicity has been demonstrated only in animals mechanisms for these effects will be discussed briefly. 

Oligonucleotide targeting to the kidney is more feasible than to many other tissues as a result of the glomerular filtration and tubular reabsorption of these poly-anionic agents. The effect is temporary allowing the therapy to be terminated when desired. Up until now, data has only been available on the kinetics and some renal and extra-renal effects of oligonucleotides in healthy animals. 

Paracetamol is a widely used analgesic, which causes liver necrosis and sometimes renal failure after overdoses in many species. The half-life is increased after overdoses because of impaired conjugation of the drug. Toxicity is due to metabolic activation and is increased in patients or animals exposed to microsomal enzyme inducers. The reactive metabolite (NAPQI) reacts with GSH, but depletes it after an excessive dose and then binds to liver protein. Cellular target proteins for the reactive metabolite of paracetamol have been detected, some of which are enzymes that are inhibited. Therefore, a number of events occur during which ATP is depleted, Ca levels are deranged, and massive chemical stress switches on the stress response. 

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