PRINCIPLES OF TOXICOLOGY - Biology East Borneo

REFERENCES AND SUGGESTED READING 143• Second, if blood flow is compromised long enough, tissue ischemia will result in irreversibleorgan damage.Nephrotoxicants, agents toxic to the nephron, the principal excretory unit of the kidney, also disruptkey life-preserving functions.• The glomerulus normally filters out the high-molecular-weight proteins from the blood.However, toxic agents will increase its permeability, allowing these proteins to appear inurine.• Agents that damage the tubular element of the nephron will compromise its ability toreabsorb solutes such as glucose and amino acids, which are necessary for normalmaintenance of the body, or disrupt sodium transport out of the nephron tubule, whichcould result in diuresis or excess urine formation or an unbalancing of the body’s ionic(salt) homeostasis.• If damage to the nephron is excessive, renal failure can decrease or completely stop urineflow, and cause death by poisoning from the body’s own products.Many agents directly toxic to the nephron are commercially or industrially important.• Mercury, lead, and cadmium are industrially the most important nephrotoxic metals.• Halogenated hydrocarbons, particularly carbon tetrachloride and chloroform, are nephrotoxic.• Certain therapeutic agents, such as phenacetin, aspirin, and the aminoglycoside antibioticsare directly nephrotoxic.Chemicals can cause nephrotoxicity indirectly:• Some agents deposit crystals in the tubular element of the nephron, resulting in physicaldamage.• Hemolytic agents such as arsine gas are capable of pigment neuropathy by releasinghemoglobin into the blood.REFERENCES AND SUGGESTED READINGAmerican Conference of Governmental Industrial Hygienists, TLVs and Other Occupational Exposure Values—1998, ACGIH, Cincinnati, OH, 1997.Agency for Toxic Substances and Disease Registry, Toxicological Profiles on CD-ROM, CRC Press, Boca Raton,FL, 1997.Berndt, W. O., “Renal Methods of Toxicology,” in Principles and Methods of Toxicology, A. W. Hayes, eds., RavenPress, New York, 1982, pp. 447–474.Brenner, B., and F. Rector, The Kidney, Saunders, Philadelphia, 1976. Ganong, F., Review of Medical Physiology,Lange Medical Publications, Los Altos, CA, 1973, pp. 510–532.Goldstein, R., and R. Schnellman, “Toxic responses of the kidney,” in Casarett and Doull’s Toxicology: The BasicScience of Poisons, 5th ed., C. D. Klaassen, ed., McGraw-Hill, New York, 1996, pp. 417–442.National Institute for Occupational Safety and Health, NIOSH Criteria Documents on CD-ROM, CDC-NIOSH,Cincinnati, 1996.Pitts, R., The Physiology of the Kidney and Body Fluids, 2nd ed., Year Book Medical Publications, Chicago, 1968.Porter, G. A., and W. A. Bennett, “Toxic nephropathies,” in B. M. Brenner, and F. C. Rector, eds., The Kidney, 2nded., Vol. II, Saunders, Philadelphia, 1981.Ullrich, K., and D. Marsh, “Kidney, water, and electrolyte metabolism,” Ann. Rev. Physiol., 25: 91 (1963).Weiner, I., “ Mechanisms of drug absorption and excretion: The renal excretion of drugs and related compounds,”Ann. Rev. Pharmacol. 7: 39 (1967).