Peroxisome Proliferators: Their Biological and Toxicological Effects

Abstract

One of the most rapidly developing areas of organelle biology, which has a major involvement in biochemical pharmacology, is the research into the peroxisomal function. There is a large group of compounds that are capable of inducing liver enlargement, proliferation of peroxisomal structures, and induction of peroxisomal and extraperoxisomal fatty acid-oxidizing enzymes in rodent liver, called peroxisome proliferators. This list includes hypolipidemic drugs, analgesics, uricosuric drugs, environmental pollutants, phthalates, etc. Some peroxisome proliferators have also been shown to increase the incidence of liver tumors. This review describes the characteristics of peroxisome proliferation in rodent liver and gives examples of different classes of chemicals that produce this effect. Mechanisms of initiation of peroxisome proliferation in rodent hepatocytes, including peroxisome proliferator-activated receptors, are also described. Rodent peroxisome proliferators are not considered to be genotoxic agents. Proposed mechanisms of liver tumor formation include induction of sustained oxidative stress, enhanced cell replication, promotion of spontaneous preneoplastic lesions, and inhibition of apoptosis. In addition, the absence of effects of peroxisome proliferators on peroxisome proliferator-associated parameters supports the hypothesis that human liver cells are refractory to peroxisome proliferator-induced hepatic carcinogenesis.

A54 peptide-mediated functionalized gold nanocages for targeted delivery of DOX as a combinational photothermal-chemotherapy for liver cancer

“…So the contents of UREA and CREA are the most common and economic indicator used to detect kidney injury. 41,42 Animal experimental results showed that our drug carrier HTPAuNCs did not cause obvious inflammatory reaction, liver toxicity, and kidney toxicity within the treatment period (Table 1), which were consistent with the experimental results in vitro.…”

“…41 Animal experimental results demonstrated that the content of TNF-α of the HTPAuNCs group had no significant increase compared with the NS group (Table 1). In addition, the dysfunction of the kidney will make the concentration of renal tubular solution increased and the renal tubular epithelial cells damaged.…”

Cytomorphological alterations of the thymus, spleen, head‐kidney, and liver in cardinal fish (Apogonidae, Teleostei) as bioindicators of stress

“…Such fattening, especially when accompanied by multiplication of peroxysomes, interrupts the normal functioning of the hepatocytes, and can, according to Suga (2004), establish circumstances leading to selective growth of neoplastic cells, and thus to formation of benign or malignant tumors. Cajaraville et al (2003), too, argued that the exposure of shallow water organisms to polychlorinated aromatic compounds, polychlorinated biphenoles, and a variety of other pollutants could cause massive damage to organs of marine organisms, inducing intensive peroxysome formation in the liver of fishes and carcinogenesis (see also Dzhekova-Stojkova et al, 2001). As demonstrated by Feldstein et al (2003), the sediment of the northern, polluted site contains numerous organic pollutants of the benzoic and phenolic groups, as well as others, which when incorporated into the local food chain of the fishes may act as triggers of peroxidaseformation and thus cytological malfunction.…”

Type 2 transglutaminase is involved in the autophagy-dependent clearance of ubiquitinated proteins

“…22,23 Peroxisomes are known to increase in their number and size, in response to a class of chemically unrelated substances, called peroxisome proliferators; when their administration is discontinued, the liver peroxisomal population rapidly decreases and readily returns to the preproliferation status due to autophagy-mediated clearance. 21,24 We chose a model of inducing peroxisomal proliferation by dietary administration of ciprofibrate. Excess liver peroxisomes are normally degraded within a week, but this rapid removal is impaired in autophagy-deficient liver.…”