Reaction of the Liver upon Long-Term Treatment of Fluoxetine and Atorvastatin Compared with Alcohol in a Mouse Model

Background. Alcoholism is known to cause liver toxicity and is extensively researched. On the other hand, stress, depression, and obesity are interrelated conditions with alcoholism, and their medications would affect the liver itself. In this study, we investigated the effects of the drugs fluoxetine and atorvastatin on the liver and compared with those of alcohol in a mouse model. Methods. Comparisons of animals treated with the three drugs were carried out: serum aspartate transaminase (AST), alanine transaminase (ALT), and albumin were measured; liver tumor necrosis factor alpha (TNF alpha) and transforming growth factor beta (TGF beta-1) levels were evaluated; proliferative cells were detected via immunohistochemistry (IHC) targeting on proliferating cell nuclear antigen (PCNA) and minichromosome maintenance complex component 2 (MCM2); for apoptosis, IHC targeting on activated caspase-3 and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) were employed; and histopathology was also documented in all groups. Results. For ALT, AST, albumin, and liver TNF alpha, only the ethanol group surged to significantly higher levels. For TGF beta-1, both ethanol and atorvastatin groups reached a significantly higher level. PCNA and MCM2 showed increased proliferation in the livers of all three groups, with the ethanol group having the highest number of positive cells followed by atorvastatin and then the fluoxetine group. As for cell death, both ethanol and fluoxetine groups showed significantly more apoptosis than control in TUNEL and activated caspase-3, while in the atorvastatin group, activated caspase-3 positive cells increased significantly, but the increase in TUNEL-positive cells did not reach statistical significance.

Malathion-Induced Hematoxicity and Its Recovery Pattern in Barbonymus gonionotus

An experiment was conducted to assess malathion-induced hematological responses of Barbonymus gonionotus (silver barb) and its recovery patterns in malathion-free water. Fish (45 days old) were exposed to two sublethal concentrations, namely, 25% and 50% (i.e., 3.78 and 7.56 ppm) of LC50 (15.13 ppm) of malathion for 28 days, followed by a postexposure recovery period for the same time. The hematological parameters were examined after 1, 7, 14, 21, and 28 days of exposure as well as after the postexposure recovery time. Except in the case of the control group (0% of malathion), the obtained results revealed that malathion exposure resulted in significantly ( p < 0.05 ) higher prevalence and severity of micronucleus and lower values of Hb, PCV, and RBC and significantly higher values of WBC in a concentration- and time-dependent manner. The values of blood glucose, MCV, MCH, and MCHC showed mixed trends during the experiment. During the recovery period, all blood parameters (micronucleus, glucose, Hb, PCV, RBC, WBC, MCV, MCH, and MCHC) partially recovered, which means that the recovery period was not long enough for the organisms to recover from the previous exposure. The study thus confirms that hematology is a sensitive indicator for fish to detect toxicity caused by different chemicals. Changes in these parameters can provide useful information about environmental conditions and risk assessment of aquatic organisms.

Clothianidin and Thiacloprid Mixture Administration Induces Degenerative Damage in the Dentate Gyrus and Alteration in Short-Term Memory in Rats

Neonicotinoids are pesticides that act as agonists of nicotinic receptors for acetylcholine in insects’ central nervous system (CNS). Chronic exposure to neonicotinoids in humans is related to autism, memory loss, and finger tremor. In this article, we evaluate the effect of subchronic oral administration of two neonicotinoids in the same mixture: clothianidin and thiacloprid. Decreasing doses of both pesticides were administered to rats starting from the lethal dose 50 (LD50) reported by the manufacturer. Our results indicate that the administration of three doses of decreasing amounts of LD50 (5/10, 4/10, and 3/10 LD50) resulted in 100% death in all cases. Ten administration times of 2/10 LD50 of the mixture caused only 20% of death cases after twenty-seven days, which was determined as a subchronic administration scheme. The animals administered 2/10 LD50 showed behavioral alterations after the first and second administration. Electrographic studies showed abnormal discharge patterns in the CNS. 72 h after the tenth dose, learning and memory tests were performed in the Morris water maze. Our results revealed significant decreases in permanence at the quadrant and the number of crosses ( P = 0.0447 , P = 0.0193 , respectively), which represent alterations in the short-term memory test, but there were no significant changes in a long-term memory test. Likewise, the brains of these animals showed tissue architecture loss, nucleosomal retraction, and a significant increase in the pycnosis of the granular neurons of the dentate gyrus analyzed at 72 h after the last dose ( P = 0.0125 ). Toxic effects and cognitive deterioration that have been found in communities living near contaminated areas are probably related to the agricultural use of neonicotinoids.

Genotoxicity Assessment and Protective Effect of Anogeissus leiocarpus Roots against Cyclophosphamide-Induced DNA Damage In Vivo

Background. Belonging to the family of Combretaceae, the roots of Anogeissus leiocarpus are traditionally used to treat diabetes, wounds, infections, pain, and gastrointestinal diseases. To our knowledge, no genotoxicity assessment of the plant was reported. Hence, this study was designed to evaluate the potential genotoxic and protective effects of extract of Anogeissus leiocarpus roots using the micronucleus test on mice bone marrow cells in vivo. Methods. Three different concentrations (250, 500, and 1000 mg·kg−1) of hydroalcoholic extract of roots of A. leiocarpus were administered daily for 7 days per os to mice, and the genotoxicity was induced by the administration ip of cyclophosphamide. Genotoxicity and cytotoxicity were evaluated by counting, respectively, the number of micronucleated polychromatic erythrocytes and polychromatic erythrocytes to total erythrocytes in the bone marrow of mice. Results. The administration of A. leiocarpus did neither increase the ratio of the polychromatic erythrocyte (PCE) nor the frequency of micronucleated PCE (MNPCE) significantly in the bone marrow cells of the mice, compared to the vehicle control animals. However, a significant increase in the incidence of MNPCE in the bone marrow cell of the cyclophosphamide-treated mice was found. Moreover, in the groups treated with the total extract of A. leiocarpus at different doses plus cyclophosphamide, there was a significant decrease p < 0.0001 in MNPCEs compared to the positive controls, in a dose-dependent manner. Conclusion. This first finding reports that the extract of A. leiocarpus was neither genotoxic nor cytotoxic. However, it shows a protective effect against the genotoxicity and cytotoxicity induced by cyclophosphamide.

Hydration with Mannitol and Dextrose May Promote Cisplatin-Induced Nephrotoxicity: Test of Five Protocols of Hydration during Cisplatin Therapy in Rat Models

Backgrounds. Cisplatin (CP) still is a novel choice for solid tumor therapy, but it is accompanied with the side effect of nephrotoxicity. Hydration may reduce the risk of CP-induced nephrotoxicity, while the issue is still challenging. In this study, five types of hydration protocols including saline, mannitol, dextrose saline, saline plus furosemide, and saline plus mannitol were examined in both sexes of rats during CP therapy. Methods. Seventy-six male and female Wistar rats in 14 groups of experiments were subjected to CP therapy, and five types of hydration protocols were implemented, and the induced nephrotoxicity was evaluated via biochemical markers, kidney function parameters, and pathology investigation. Results. Male and female rats had different responses to hydration protocol types. The higher mortality rate was seen in female rats that received mannitol or dextrose hydration types. In addition, the serum levels of blood urea nitrogen (BUN) and creatinine (Cr) and sodium excretion fraction (ENa%) increased and the clearance of Cr (ClCr) decreased significantly ( P < 0.05 ) in female rats hydrated with saline plus furosemide or mannitol plus saline-treated groups. The worsened condition in male rats is observed in the mannitol hydration group with a significant decrease of ClCr and significant increase of serum BUN and Cr and ENa% ( P < 0.05 ). The higher kidney tissue damage score (KTDS) in the mentioned groups verified the findings. Conclusion. Hydration with mannitol or dextrose promotes the risk of nephrotoxicity during CP therapy with more intensity on the female.

Nanonaringenin and Vitamin E Ameliorate Some Behavioral, Biochemical, and Brain Tissue Alterations Induced by Nicotine in Rats

Nicotine is the major alkaloid present in cigarettes that induces various biochemical and behavioral changes. Nanonaringenin (NNG) and vitamin E are antioxidants that are reported to mitigate serious impairments caused by some toxins and oxidants. Thus, we aimed to investigate the efficacy of NNG, vitamin E, and their combinations to ameliorate behavioral, biochemical, and histological alterations induced by nicotine in rats. Adult male albino rats were randomly grouped into six equal groups (10 rats/group): control, N (nicotine 1 mg/kg b.w./day S/C from 15th to 45th day, 5 days a week), NNG (25 mg/kg b.w./day orally for 45 days), N + NNG, N + E (nicotine + vitamin E 200 mg/kg b.w./day orally), and N + NNG + E (nicotine + NNG + vitamin E at the aforementioned doses). Behavioral tests were conducted on day 15 and 30 postnicotine injection, while memory tests, brain neurotransmitters, antioxidants, and histopathological examination were examined at day 30 only. As a result, nicotine impaired rats’ activity (hypoactivity and hyperactivity) and memory, induced anxiolytic and anxiogenic effects on rats, and altered neurotransmitters (acetylcholinesterase, serotonin, and dopamine), and redox markers (MDA, H2O2, GSH, and catalase) levels in brain homogenates. Thickening and congestion of the meninges and degeneration of the cerebral neurons and glia cells were observed. Cosupplementation with NNG, vitamin E, and their combination with nicotine was beneficial in the alleviation of activity impairments and improved short memory and cognition defects and exploratory behaviors. Our results indicate the antioxidant potential of NNG and vitamin E by modulating redox markers and neurotransmitters in the brain. Thus, data suggest that the prophylactic use of NNG, vitamin E, and/or their combination for (45 days) may have a successful amelioration of the disrupted behavior and cognition and biochemical and histopathological alterations induced by nicotine.

Potential Impacts of Climate Change on the Toxicity of Pesticides towards Earthworms

This review examined one of the effects of climate change that has only recently received attention, i.e., climate change impacts on the distribution and toxicity of chemical contaminants in the environment. As ecosystem engineers, earthworms are potentially threatened by the increasing use of pesticides. Increases in temperature, precipitation regime changes, and related extreme climate events can potentially affect pesticide toxicity. This review of original research articles, reviews, and governmental and intergovernmental reports focused on the interactions between toxicants and environmental parameters. The latter included temperature, moisture, acidification, hypoxia, soil carbon cycle, and soil dynamics, as altered by climate change. Dynamic interactions between climate change and contaminants can be particularly problematic for organisms since organisms have an upper and lower physiological range, resulting in impacts on their acclimatization capacity. Climate change variables such as temperature and soil moisture also have an impact on acidification. An increase in temperature will impact precipitation which might impact soil pH. Also, an increase in precipitation can result in flooding which can reduce the population of earthworms by not giving juvenile earthworms enough time to develop into reproductive adults. As an independent stressor, hypoxia can affect soil organisms, alter bioavailability, and increase the toxicity of chemicals in some cases. Climate change variables, especially temperature and soil moisture, significantly affect the bioavailability of pesticides in the soil and the growth and reproduction of earthworm species.

Hepatoprotective Effect of Corm of Ensete ventricosum (Welw.) Cheesman Extract against Isoniazid and Rifampicin Induced Hepatotoxicity in Swiss Albino Mice

Drug-induced liver injury (DILI) is one of the cumbersome health-related problems which render approximately 50% of liver failure and patients to receiving liver transplantation every year. Antituberculosis drugs such as isoniazid and rifampicin are potentially rendering hepatotoxicity. Ensete ventricosum (Welw.) Cheesman is an herbaceous perennial plant that contributes to the indigenous ethnomedicinal values for the society. This study aimed to investigate the hepatoprotective effect of corm of Ensete ventricosum (Welw.) Cheesman extracts against isoniazid and rifampicin induced hepatotoxicity in Swiss albino mice. The study was conducted on 30 Swiss albino mice randomly allocated into five groups. Group I, group II, group III, group IV, and group V were the groups in which mice were given distilled water, only isoniazid and rifampicin, isoniazid and rifampicin along with 200 mg/kg corm of Ensete ventricosum (Welw.) Cheesman extract, isoniazid and rifampicin along with 400 mg/kg corm of Ensete ventricosum (Welw.) Cheesman extract, and isoniazid and rifampicin along with silymarin per oral per day, respectively. On the 30th day of the experiment, mice were sacrificed after anesthetized, and blood was drawn for the liver function test, and the liver was also taken from each experimental mouse for histopathological evaluation. Data were entered into EpiData version 3.1 subsequently exported to SPSS version 25 for analysis by using one-way ANOVA. Plasma alanine aminotransferase (ALT) levels, aspartate aminotransferase (AST), alkaline phosphatase (ALP), and total bilirubin (TBIL) of group II mice were significantly ( p < 0.05 ) elevated as compared to group I. The group of mice treated with a corm of Ensete ventricosum (Welw.) Cheesman at a dose of 400 mg/kg (group IV) and silymarin100 mg/kg (group V) showed a significant ( p < 0.05 ) decrease in ALT, AST, ALP, and TBIL as compared to the group II. The liver section of group II showed a change in liver architecture; however, these deformities were not noticed in group IV mice. The result showed corm of Ensete ventricosum (Welw.) Cheesman extract has a very promising hepatoprotective potential against isoniazid and rifampicin induced liver injury.

Role of Autophagy in Cadmium-Induced Hepatotoxicity and Liver Diseases

Cadmium (Cd) is a toxic pollutant that is associated with several severe human diseases. Cd can be easily absorbed in significant quantities from air contamination/industrial pollution, cigarette smoke, food, and water and primarily affects the liver, kidney, and lungs. Toxic effects of Cd include hepatotoxicity, nephrotoxicity, pulmonary toxicity, and the development of various human cancers. Cd is also involved in the development and progression of fatty liver diseases and hepatocellular carcinoma. Cd affects liver function via modulation of cell survival/proliferation, differentiation, and apoptosis. Moreover, Cd dysregulates hepatic autophagy, an endogenous catabolic process that detoxifies damaged cell organelles or dysfunctional cytosolic proteins through vacuole-mediated sequestration and lysosomal degradation. In this article, we review recent developments and findings regarding the role of Cd in the modulation of hepatotoxicity, autophagic function, and liver diseases at the molecular level.

Toxicity of Nanoparticles in Biomedical Application: Nanotoxicology

Nanoparticles are of great importance in development and research because of their application in industries and biomedicine. The development of nanoparticles requires proper knowledge of their fabrication, interaction, release, distribution, target, compatibility, and functions. This review presents a comprehensive update on nanoparticles’ toxic effects, the factors underlying their toxicity, and the mechanisms by which toxicity is induced. Recent studies have found that nanoparticles may cause serious health effects when exposed to the body through ingestion, inhalation, and skin contact without caution. The extent to which toxicity is induced depends on some properties, including the nature and size of the nanoparticle, the surface area, shape, aspect ratio, surface coating, crystallinity, dissolution, and agglomeration. In all, the general mechanisms by which it causes toxicity lie on its capability to initiate the formation of reactive species, cytotoxicity, genotoxicity, and neurotoxicity, among others.