The environmental and human effects of ptaquiloside-induced enzootic bovine hematuria: a tumorous disease of cattle.

In this review, we address the major aspects of enzootic bovine hematuria and have placed special emphasis on describing the etiology, human health implications, and advanced molecular diagnosis of the disease.Enzootic bovine hematuria (EBH) is a bovine disease characterized by the intermittent presence of blood in the urine and is caused by malignant lesions in the urinary bladder. This incurable disease is a serious malady in several countries across many continents. Accurate early-stage diagnosis of the disease is possible by applying advanced molecular techniques, e.g., detection of genetic mutations in the urine of cows from endemic areas. Use of such diagnostic approaches may help create an effective therapy against the disease.There is a consensus that EBH is caused primarily by animals consuming bracken fern (P. aquilinum) as they graze. The putative carcinogen in bracken is ptaquiloside(PT), a glycoside. However, other bracken constituents like quercetin, isoquercetin,ptesculentoside, caudatoside, astragalin, and tannins may also be carcinogenic.Studies are needed to identify the role of other metabolites in inducing urinary bladder carcinogenesis.The bovine papilloma virus is also thought to be an associated etiology in causing EBH in cattle. There is growing alarm that these fern toxins and their metabolites reach and contaminate the soil and water environment and that the carcinogen (PT)is transmitted via cow's milk to the human food chain, where it may now pose a threat to human health. An increased incidence of gastric and esophageal cancer has been recorded in humans consuming bracken ferns, and among those living for long periods in areas infested with bracken ferns.Although preliminary therapeutic vaccine trials with inactivated BPV-2 against EBH have been performed, further work is needed to standardize and validate vaccine doses for animals.