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Two new molecules (1E,3E)-1,4-bis(1-naphthyl)-2,3-dinitro-1,3-butadiene (1-Naph-DNB) and (2Z,4E)-2-methylsulfanyl-5-(1-naphthyl)-4-nitro-2,4-pentadienoate (1-Naph-NMCB) in previous studies showed interesting antiproliferative activity in vitro. Furthermore, toxicological tests and histological analysis provided promising results, in particular for 1-Naph-NMCB that displayed lower toxic activity both in terms of lethal effect and tissue damage of the main organs. Finally, studies of the antitumour activity in vivo confirmed the efficacy of both molecules, though with some differences in tumour selectivity and levels of activity. In this investigation the activities of some specific enzymes, acid phosphatase (AcPase), alkaline phosphatase (AlkPase), catalase (Cat), succinic dehydrogenase (SDH), glucose-6-phosphatase (G6Pase) and K+ p-nitrophenyl phosphatase (K+ pNPPase) were studied in the liver and kidney as histopathological biomarkers, to assess the effects of the two compounds in organs generally involved in the metabolism and excretion of different drugs. As oxidative stress may also develop as a consequence of the toxic effect of chemicals, reactive oxygen species (ROS) production was evaluated by a histochemical method. The results indicated that some enzyme activities and ROS expression changed in a dose-related manner. Nevertheless, neither in the liver nor in the kidney were dramatic toxic effects evident. By contrast, the variations of some enzyme activities (AlkPase, AcPase, Cat, K+ pNPPase) were interpreted as possible defensive mechanisms for tolerating high dosage of the compounds.

Iron is indispensable for the metabolism and proliferation of both normal and malignant cells. Recycling from senescent erythrocytes in the liver and spleen is critical for iron supply to all tissues. In the liver and spleen from MMTV-neu (erbB-2) mice bearing a mammary carcinoma, we noticed the scarcity of hemosiderin pigment and its abundance in the stroma of the tumor. Thus iron (III) was investigated with the Perls' reaction in tissues from normal and MMTV-neu mice. With respect to normal animals, in MMTV-neu mice, staining for iron was almost absent in the liver and scarce in the red pulp of the spleen. By contrast, iron was abundant in stromal and tumor cells in the invasion, angiogenic, necrotic and hemorrhagic regions and also in the interstitial fluid. These observations suggest that the tumor subverts iron recycling to its own advantage, by directly utilizing iron released from erythrocytes and dead tumor cells. Our findings are in keeping with the development of iron chelating drugs as chemotherapic agents.

In a previous investigation, reperfusion with a melatonin-containing medium was demonstrated to enhance bile production and tissue ATP levels in rat livers, cold-preserved with University of Wisconsin (UW) or Celsior solutions, with respect to melatonin-free reperfusion; lipid peroxidation products in the perfusate were not influenced by the indole. This was ascribed to an increased efficiency of the hepatocyte mitochondria induced by melatonin. Reactive oxygen species (ROS) normally leak from the electron transfer chain in mitochondria and excessive ROS production is presumed to mediate ischemia-reperfusion (I/R) damage. A histochemical reaction was used to demonstrate ROS on the same model. Compared to the lobular zonation of ROS in control livers, the stained area of cold-preserved livers reperfused without melatonin was restricted to a narrow portal region, in keeping with the much lower ATP content. When reperfusion was performed with melatonin, the liver morphology was improved and the ROS reaction in hepatocytes more intense, though not reaching the control liver pattern. Sinusoidal cells were poorly-stained in both cases. In conclusion, with this different approach, melatonin was confirmed to improve mitochondrial performance and to discriminate parenchymal from sinusoidal cell behavior. Our observations confirm that melatonin mitigates I/R injury and support its potential in liver transplantation.

Background: The class 1 antiarrhythmic drug procainamide hydrochloride might protect against acute cisplatin-induced nephrotoxicity and hepatotoxicity in mice and rats. In this report, the protective activity of procainamide hydrochloride against renal and hepatic tissue damage induced by repeated administration of low doses of cisplatin was analyzed morphologically and histochemically., Materials and Methods: Light microscopy observations were performed on liver, renal and heart samples obtained from female Wistar rats treated twice a week for 10 weeks with 1 mg/kg cisplatin (cumulative dose: 20 mg/kg), with or without 100 mg/kg procainamide hydrochloride (cumulative dose: 2 g). Samples were then submitted to histochemical stainings [i.e. H & E, periodic acid Schiff (PAS) and Sudan Black]., Results: Light microscopy analysis revealed that the coadministration of cisplatin and procainamide hydrochloride significantly reduced tissue alterations both in the kidneys and liver, while in the heart, neither cisplatin nor the combination of cisplatin and procainamide hydrochloride caused any evident tissue damage., Conclusion: The morphological and histochemical data confirm that procainamide hydrochloride is able to protect not only from acute cisplatin-induced toxicities, but also from tissue alterations induced in the liver and kidneys by the administration of repeated low doses of cisplatin.