Previous studies have shown the toxic effects of formaldehyde (HCHO) on the skin and eyes, and on the respiratory, gastrointestinal, nervous, and reproductive systems
7-10. In addition to its deleterious effects on histological structure and functions of the liver, HCHO has been reported to cause a decrease in liver weight
12,13 and damage to the biliary ducts
14.
In our study, the light microscopic evaluation of the liver tissue sections revealed enlarged sinusoids filled with blood and cellular infiltration in the portal area and around vena centralis. Furthermore, some hepatocytes had cytoplasmic vacuolizations, while some had hyperchromatic nuclei. Strubelt et al.15 found that HCHO exposure leads to mitochondrial destruction and damages rough endoplasmic reticulum. Beall and Ulsamer32 reported centrilobular vacuolization and local cellular necrosis in the liver associated with HCHO exposure. In their study on rats, Dumont et al.14 detected structural changes in the biliary epithelial cells after HCHO administration.
Free oxygen radicals are a result of metabolic intracellular process forming under natural conditions. They inflict oxidative damage on the cells by affecting membrane lipids, proteins, and nucleic acids. These potentially harmful effects are regulated by antioxidant defense mechanism. The antioxidant enzymes such as SOD and GSH-Px are needed for the maintenance of cellular balance and scavenging the free radicals away33. Malondialdehyde (MDA) is one of the products of lipid peroxidation and is commonly used parameter to indicate oxidative stress34.
HCHO disturbs the oxidant-antioxidant balance in various tissues and cause oxidative stress in parallel with tissue damage. In previous studies, increased MDA levels in the lung, liver, and testicular tissues of the rats exposed to HCHO were reported34-36. In accordance with our findings, Strubelt et al.15 have reported increased MDA levels in the liver tissues of HCHO-exposed animals. Similarly, Teng et al.37 in their experimental study on isolated rat hepatocytes showed that HCHO at low concentrations leads to oxidative stress.
Skrzydlewska and Farbiszewski38-40 noted methanol metabolized into HCHO and formic acid for the increased levels of SOD and GSH-Px levels in rat liver tissues. However, Datta and Namasivayam41 found that methanol decreases SOD levels and increases CAT and MDA levels in rat hepatocytes. In our study, SOD, GSH-Px, and CAT values increased in the HCHO-exposed rats. Increased SOD activity may be a response of increased oxidative stress in the liver tissue. CAT increase, however, may be indicative of high degree oxidative stress due to elevated endogenous H2O2. It may also be an adaptive response to oxidative stress induced by HCHO. GSH-Px is an important antioxidant enzyme acting in H2O2 elimination and lipid peroxidation. Increased GSH-Px activity suggests increased H2O2 products.
Melatonin is known to be involved in a variety of physiological processes including the regulation of endocrine rhythm, antigonadotropic effects, neuroprotective effects, stimulation of the immune system, and free radical scavenging action17,22-24. In addition to these properties of melatonin, it is a potent antioxidant agent and exerts a protective effect against oxidative stress25,42,43. In our study, melatonin was found to partially prevent the liver damage against HCHO intoxication. The exact mechanism of melatonin-provided prevention of hepatic damage induced by formaldehyde is not completely clear. Considering the distinctive properties of melatonin and the results of the present study, it is plausible that both its radical-scavenging and antioxidant actions are involved in preventing tissue damage.
We concluded that chronic exposure of formaldehyde causes structural degeneration and oxidative damage in the liver of rats. We also concluded that melatonin exerts a beneficial effect against formaldehyde toxicity in the liver appeared to be due to its antioxidant and free radical scavenger activity.
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