The Use of Tannic Acid in the Local Treatment of Burn Wounds: Intriguing Old and New Perspectives

Wounds. 2001;13(4) 

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Tannic Acid and Liver Necrosis

In 1938, Wilson, MacGregor, and Stewart[28] were the first to report on the occurrence of liver lesions in tannic acid-treated burn patients. Post-mortem examination in a series of 33 severely burned, fatal cases revealed a characteristic degeneration and necrosis of liver cells, which was much more intense than that seen in other organs. In its mildest form, it appeared as a fatty degeneration of the epithelial cells surrounding the veins in the central zone of the hepatic lobules but could, in more advanced examples, progress to a total destruction of the central zones in which only a narrow strip surrounding each portal tract showed surviving liver cells. In subsequent years, several other communications were published describing liver damage in burn patients who had some form of tannic acid therapy. Buis and Hartman[32] confirmed the findings by Wilson, et al.,[28] and, in addition, noted that the lesions in humans were identical to those found in experimentally burned animals treated with tannic acid jelly. Belt[94] reported histopathological changes that closely resembled those of yellow fever. McClure,[78] McClure and Lam,[31] and Duffin[95] observed the clinical signs of a marked jaundice and decreased liver function accompanied by central liver necrosis in some patients who failed to survive. Evidence of an impaired liver function has also been reported by others. Wolff, Elkinton and Rhoads,[96] as well as Abbott and Holden[97] found an elevation of blood bilirubin, impairment of glycogenesis and hippuric acid synthesis, and a decrease in prothrombin levels. However, none of these authors associated the phenomena seen in burn patients with the application of tannic acid but merely suggested it to be a consequence of toxemia and the circulation of burn toxins.

Only in 1942, Wells, Humphrey, and Coll[34] directly related the occurrence of liver damage to the tannic acid therapy. In their article in the New England Journal of Medicine, these authors described four patients who died three to five days after the injury, in the period which was generally associated with toxemia. In agreement with previous observations, on autopsy these patients exhibited central lobular liver necrosis as the outstanding feature or as the sole cause of death. Since the common denominator appeared to be the employment of tannic acid in these cases, the possible role of this constituent in the production of hepatic damage was further investigated. For this purpose, a series of experiments was performed in which rats were subcutaneously injected with different doses of tannic acid. This induced liver damage that was essentially similar to the lesions in humans and was proportional to the amount of tannic acid administered. Therefore, it was concluded that the liver damage seen in burn patients might be due to tannic acid poisoning and that it should be distinguished from the patient's toxemic phase, which resulted from the resorption of toxins from the burn wound.[34]

Following the experiments by Wells and coworkers, additional evidence was accumulated for the detrimental effects of tannic acid. The occurrence of hepatotoxic signs in tannic acid-treated burn patients was confirmed by several other clinicians.[50,51,98,99,100,101,102] The hepatotoxic signs were also related to the increase in the frequency of liver necrosis seen in fatal burns[103,104] and the comparable higher mortality rates as found in some late clinical trials (Figure 1).[101,105] Also, experimental data from animal studies provided further support for its harmfulness. Subcutaneous injection of tannic acid gave a disturbed liver function[106,107] and a fairly uniform and specific liver necrosis.[108,109,110,111] Intramuscular injections resulted in a slight, though definite, liver damage.[112] Intravenous injections produced severe liver lesions in mice[109,112] and more variable pathological changes in rabbits.[106] When tannic acid was applied to denuded skin surfaces, the amount of liver damage seemed to be dependent on the application form and the type of animal. An aqueous solution or an ointment usually produced hepatic necrosis in rats, whereas no lesions could be found when tannic acid was combined with silver nitrate.[108] Dogs treated with tannic acid jelly showed congestion, fatty degeneration, and myelinization of the liver but no central necrosis.[111] Application of tannic acid to denuded surfaces was lethal for mice but not for rats or rabbits.[107] Neither was liver damage, as measured by the Bromsulphalein test, seen in rabbits.[107] A comparable variation in the degree of liver damage was found when tannic acid was applied to experimentally induced burns. In guinea pigs there was only slight liver damage,[112] and burned dogs showed clinical jaundice and central liver necrosis in just a limited number of cases.[111] Conversely, varying degrees of liver damage were observed in goats and rabbits, although this was in no case as severe as after subcutaneous injection.[109]

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