Hepatotoxic effects of melamine exposure from the weaning period in rats: a flow cytometric, electron microscopic, and histopathologic study

Abstract

This study aims to investigate the effects of melamine exposure from the weaning period (21st postnatal days in rats) on liver tissue. Female Wistar albino rats (n = 18) were divided into three groups. About 0.1-ml saline was applied to the control group by gavage for 21 days from the postnatal 21st day. The second group was taken 50-mg/kg melamine (in 0.1-ml saline) and the third group was taken 75-mg/kg melamine (in 0.1-ml saline) p.o. On the postnatal 45th day, all rats were sacrificed under anesthesia. Then, liver tissues were cut into three parts and two of them placed in neutral formalin for histopathological and flow cytometric analysis, and one of them placed in 2.5% glutaraldehyde. Histopathological analysis was performed with hematoxylin & eosin, Masson trichrome, periodic acid Schiff stained sections, and also with transmission electron microscopy. Apoptosis (Annexin V positivity) was analyzed by flow cytometry. According to histopathological analysis, hepatocyte damage, sinusoidal dilatation, and inflammatory cell infiltration significantly increased in both melamine groups compared with the control group. Apoptosis significantly increased in the 50 and 75-mg melamine groups compared with the control group. In the results of transmission electron microscopy analysis, there was abnormal chromatin distribution in the hepatocyte nuclei, loss in the cristae of the mitochondria, and organelle loss in large areas in the cytoplasm in both melamine exposure groups. As result, melamine exposure from the weaning period causes liver damage with increasing doses.

Nootkatone Mitigated Melamine-Evoked Hepatotoxicity by Featuring Oxidative Stress and Inflammation Interconnected Mechanisms: In Vivo and In Silico Approaches

“…In addition, researchers [ 29 ] reported an accumulation of hepatic aggregates and disruption of hepatic structure following ML exposure. This observation was also reported in previous studies [ 2 , 10 , 11 ], demonstrating that ML clearly disrupts rat liver tissue.…”

“…It is widely dispersed in the environment including water and soil [ 30 ], and has been incriminated as a substance in food adulteration [ 31 ]. The liver is the primary organ for metabolism and detoxification and one of the organs most seriously affected by ML exposure [ 10 , 29 ].…”

“…Zhang and colleagues [ 9 ] found that ML was able to induce DNA damage in sperm with a significant increase in sperm abnormality rates in exposed mice. ML residues accumulate in different organs after intravenous administration, causing toxic effects in the brain, spleen, bladder, and kidney [ 10 ]. ML also damages the liver, the chief site for detoxification and elimination in the body [ 10 ].…”

“…ML residues accumulate in different organs after intravenous administration, causing toxic effects in the brain, spleen, bladder, and kidney [ 10 ]. ML also damages the liver, the chief site for detoxification and elimination in the body [ 10 ]. Previous investigations have reported that ML induced significant alterations in hepatic histoarchitecture and elevated liver function markers, as well as the induction of oxidative stress, inflammation, and apoptotic changes [ 2 , 11 , 12 ].…”

Screening and prioritising Persistent, Mobile and Toxic chemicals: development and application of a robust scoring system

“…When there is relevant and reliable experimental evidence available, this should be used to overrule one or more of these scores. For example, for melamine, the recently identified hepatoxic effects of melamine are not picked up by the QSARs, which would justify a higher T-score [48]. Another example is the low P-score for 1,4-dioxane, which can be overruled by the empirical evidence as provided e.g.…”