Cisplatin, doxorubicin and fluorouracil (5-FU), drugs belonging to different chemical classes, have been extensively used for chemotherapy of various cancers. Despite extensive investigations into their hepatotoxicity, there is very limited information on their effects on the structure and ultra-structure of liver cells in vivo. Here, we demonstrate for the first time, the effects of these three anticancer drugs on rat liver toxicity using both light and electron microscopy. Light microscopic observations revealed that higher doses of cisplatin and doxorubicin caused massive hepatotoxicity compared to 5-FU treatment, including dissolution of hepatic cords, focal inflammation and necrotic tissues. Interestingly, low doses also exhibited abnormal changes, including periportal fibrosis, degeneration of hepatic cords and increased apoptosis. These changes were confirmed at ultrastructural level, including vesiculated rough endoplasmic reticulum and atrophied mitochondria with ill-differentiated cisternae, dense collection of macrophages and lymphocytes as well as fibrocytes with collagenous fibrils manifesting early sign of fibrosis, especially in response to cisplatin and doxorubicin -treatment. Our results provide in vivo evidence, at ultrastructural level, of direct hepatotoxicity caused by cisplatin, doxorubicin and 5-FU at both light and electron microscopi. These results can guide the design of appropriate treatment regimen to reduce the hepatotoxic effects of these anticancer drugs.

The role of oxidative stress in chronic cadmium (Cd) toxicity and its prevention by cotreatment with β‐carotene was investigated. Adult male rats were intragastrically administered 2 mg CdCl2/kg body weight three times a week intragastrically for 3 and 6 weeks. Brain and testicular thiobarbituric acid reactive substances (TBARS) was elevated after 3 and 6 weeks of Cd administration, indicating increased lipid peroxidation (LPO) and oxidative stress. Cellular damage was indicated by inhibition of adenosine triphosphatase (ATPase) activity and increased lactate dehydrogenase (LDH) activity in brain and testicular tissues. Chronic Cd administration resulted in a decline in glutathione (GSH) content and a decrease of superoxide dismutase (SOD) and glutathione S‐transferase (GST) activity in both organs. Administration of β‐carotene (250 IU/kg i.g.) concurrent with Cd ameliorated Cd‐induced LPO. The brain and testicular antioxidants, SOD, GST, and GSH, decreased by Cd alone, were restored by β‐carotene cotreatment. Concurrent treatment with β‐carotene also ameliorated the decrease in ATPase activity and the increase in LDH activity in brain and testis of Cd‐treated rats, indicating a prophylactic action of β‐carotene on Cd toxicity. Therefore, the results indicate that the nutritional antioxidant β‐carotene ameliorated oxidative stress and the loss of cellular antioxidants and suggest that β‐carotene may control Cd‐induced brain and testicular toxicity. © 2000 John Wiley & Sons, Inc. J Biochem Toxicol 14:238–243, 2000

The present study aimed to determine the effects of zinc oxide nanoparticles (ZnO-NPs), thyme oil (THO), or their combination on the nutrient digestibility coefficients, reproductive parameters, and some blood metabolites of male Californian rabbits. One hundred rabbits, 29-weeks of age (initial body weight 3.48 ± 0.08 kg) were randomly distributed into four groups, 25 rabbits each. Treatment groups were fed a control diet, a control diet supplemented with ZnO-NPs (100 mg/kg), THO (500 mg/kg), or combination of ZnO-NPs (100 mg/kg) and THO (500 mg/kg). The feeding trial lasted for 35 days. Results showed improvements in dry matter, crude protein, ether extract, and crude fiber in ZnO-NPs, THO, and their combination treated groups compared to those of control. Furthermore, semen volume, sperm motility, vitality, and morphology were significantly improved (p < 0.01) in ZnO-NPs and THO groups rather than the control. Both ZnO-NPs and THO, as either individual or combined treatments significantly improved the serum alanine amino-transferase (ALT), aspartate amino-transferase (AST), urea, and creatinine compared to the control. Moreover, serum concentrations of testosterone were significantly increased in rabbits supplemented with ZnO-NPs, THO, or their combination compared to those of control (p < 0.05). In conclusion, ZnO-NPs, THO, or their combination improved the digestibility of nutrients, liver/ kidney functions, semen characteristics, and testosterone concentration in male rabbits.

IntroductionThe importance of Nile tilapia, Oreochromis niloticus in aqua cultures is due to its spreading in most countries of the world [1]. It breads in captivity and wide variety of water conditions [2]. Lake Manzalah (LM) is one of the most important lakes in Egypt that provides more than 70% of the total fishery of the country [3] and considered as a highly polluted with toxic heavy metals and pesticides due to progressive increase of industrial and agricultural drainage, as well as sewage out fall from the surrounding governorates [4]. The mean values of some heavy metals (Cd, Pb, Fe, Cr and Mn) recorded in LM were higher than the world permissible levels [5] and according to the Egyptian laws [6]. Such heavy metals are not lethal to fish, but concentrated in their flesh and create a hazard to the consumer [7,8]. Cd, Pb, Zn, and Cr are considered the main causes of pollution in aquatic ecosystem [9]. The serious effect of these metals is derived from their persistence, toxicity and bioaccumulation, and consequently exert dangerous problem to man [10]. Experimental studies on heavy metals proved that they could impair the respiratory functions of the gills; consequently death in fish is probably caused by tissue hypoxia [11]. Metals affect not only the fish morphology, but also all biological activities [12]. Among the heavy metals; Cd and Pb are the serious heavy metals that produce histopathological alterations including liver damage [13], respiratory dysfunctions [14], testicular and ovarian alterations [15][16][17]. These pathological alterations were primarily attributed to damage of cell membranes which allows higher uptake of Cd and Pb and thus the injury extends to more critical targets [18]. Many studies focused on bioaccumulation of heavy metals in fish and biological studies. Thus we aimed in this work to study the testicular histopathological alterations of Oreochromis niloticus using light microscope and the mature sperm using TEM. Materials and Methods Samples collectionSamples of water and 48 specimen of Nile tilapia, Oreochromis niloticus about 14-20 cm in length and 120-200 g in weight were collected from two areas; Demitta branch of RN at Mansoura city as a control site and LM as a polluted area during the spawning season from March-June and transported to the laboratory in tanks provided with oxygen pump. The fish were weighed, dissected and the testes were Abstract Background: Pollution of the aquatic environment by inorganic and organic chemicals is a major factor posing serious threat to the survival of aquatic organisms including fish. Lake Manzala (LM) is one of the Egypt's northern Delta Lakes situated on the Mediterranean Coast of the Delta. It is affected by drainage water polluted by different heavy metals that their concentrations exceed the maximum world permissible levels.