scholarly journals Hepatotoxic Assessment of Tramadol-Diclofenac Use: A Study in a Rat Model

2019 ◽  
Vol 8 (2) ◽  
pp. 41-45
Author(s):  
Elias Adikwu ◽  
Ebinyo Clemente Nelson

The concurrent use of tramadol and diclofenac may increase hepatotoxic risk due to their individual hepatotoxic effects. This study assessed the hepatotoxic effect of tramadol-diclofenac administration in albino rats. Twenty-four adult male albino rats (200-220g) randomized into four groups were orally administered with tramadol (12mg/kg/day), diclofenac (6mg/kg/day) and tramadol-diclofenac for 14 days respectively. The rats were anesthetized, blood samples were collected and evaluated for serum liver function and lipid parameters. Liver samples were weighed and evaluated for biochemical parameters and histology. The effects of tramadol-diclofenac on the body and liver weights did not differ significantly (p>0.05) when compared to control. Also, effects were not significant (p>0.05) on blood glucose, and serum cholesterol, triglyceride, low and high density lipoprotein cholesterol levels when compared to control. Liver and serum levels of aminotransferases, alkaline phosphatase, lactate dehydrogenase, gamma–glutamyl transferase, conjugated bilirubin and total bilirubin increased significantly in rats treated with tramadol (p<0.05), diclofenac (p<0.01) and tramadol-diclofenac (p<0.001) when compared to control. Furthermore, significant decreases in liver catalase, glutathione, superoxide dismutase, glutathione peroxidase levels with significant increases in malondialdehyde levels occurred in rats treated with tramadol (p<0.05), diclofenac (p<0.01) and tramadol-diclofenac (p<0.001) when compared to control. Hepatocyte necrosis was observed in rats treated with tramadol-diclofenac. Tramadol-diclofenac may increase hepatotoxic risk at doses used for this study.

Author(s):  
Elias Adikwu ◽  
Nelson Clemente Ebinyo

Background: The hepatotoxic effect of 5-fluorouracil (5-FU) can deprive cancer patients of its maximum therapeutic benefits. Selenium (Se) is a trace element with potential benefits in some animal models of diseases. Objectives: This study assessed the ability of Se to nullify the hepatotoxic effect of 5-FU in albino rats.  Methods: In this study, 40 adult male albino rats were grouped into A to D (each 5 rats). Rats in group A (control) were treated intraperitoneally (IP) with normal saline (0.2 mL) daily for 5 days. Rats in groups B1 to B3 were treated IP with Se (0.125, 0.25, and 0.50 mg/kg) daily for 5 days, respectively. Rats in group C were treated IP with 5-FU (20 mg/kg) daily for 5 days. Rats in groups D1to D3 were treated IP with Se with 0.125, 0.25, and 0.50 mg/kg before treatment with 5-FU (20 mg/kg) daily for 5 days, respectively. After treatment, the rats were euthanized, and their blood samples were collected and evaluated for serum liver function. Liver samples were evaluated for biochemical and histological parameters. Results: Liver and serum aminotransferases, gamma-glutamyl transferase, lactate dehydrogenase, alkaline phosphatase, total bilirubin, and conjugated bilirubin levels were significantly (P<0.001) high in 5-FU-treated rats in comparison to the control group. Liver glutathione peroxidase, superoxide dismutase (SOD), catalase, and glutathione levels were significantly (P<0.001) low whereas the malondialdehyde level was significantly (P<0.001) high in 5-FU-treated rats compared with the control group. Moreover, hepatocyte necrosis was observed in 5-FU-treated rats.  Conclusion: Nonetheless, 5-FU-induced hepatotoxicity was significantly nullified in rats supplemented with Se (0.125 mg/kg, P<0.05; 0.25 mg/kg, P<0.01, and 0.5 mg/kg, P<0.001) in a dose-dependent fashion in comparison to 5-FU-treated rats. Thus, Se may have a clinical benefit in 5-FU-induced hepatotoxicity


2018 ◽  
Vol 29 (1) ◽  
pp. 29-35 ◽  
Author(s):  
Olorunfemi R. Molehin ◽  
Anne A. Adeyanju ◽  
Stephen A. Adefegha ◽  
Oluwasanmi O. Aina ◽  
Blessing A. Afolabi ◽  
...  

AbstractBackground:Elevation of phosphodiesterase-5 (PDE5) activity converts cyclic guanosine monophosphate (cGMP) to 5′-GMP, a mechanism that could be associated with drug-mediated hepatotoxicity. This study investigated whether selective inhibition of PDE5 by sildenafil could offer protection against hepatotoxicity induced by carbon tetrachloride (CCl4).Methods:CCl4(0.5 mL/kg) was administered intraperitoneally to induce hepatotoxicity. The control group received normal saline. Sildenafil (5 mg, 10 mg, and 20 mg/kg, p.o.) was administered to CCl4-treated rats.Results:CCl4significantly increased the serum levels of gamma glutamyl transferase (γ-GT), alkaline phosphatase (ALP), aspartate aminotransferase (AST), and alanine aminotransferase (ALT) and reduced total protein (TP) (p<0.05). Pretreatment with sildenafil moderately reduced ALP, AST, and ALT activities with modest increase in TP level. CCl4-induced changes in the antioxidant status of the liver were significantly improved by sildenafil, especially at the lowest dose of 5 mg/kg by elevating the levels of reduced glutathione (GSH), glutathione peroxidase (GPx), catalase (CAT), superoxide dismutase (SOD), and glutathione-S-transferase (GST) and preventing lipid peroxidation (p<0.05). Sildenafil did not significantly alter the total cholesterol and triglyceride levels. However, high-density lipoprotein (HDL) level was significantly increased by sildenafil (p<0.05).Conclusions:The results from this study suggest that sildenafil, when used at low doses, may be a useful pharmacological protective agent against CCl4-induced hepatotoxicity.


Author(s):  
Elias Adikwu ◽  
Emmanuel Nnaedozie

Background: Methotrexate (MTX) is one of the frequently used chemotherapeutic agents, especially in hematological malignancies and solid tumors. Objectives: MTX hepatotoxicity symptoms range from elevations in serum aminotransferases to hepatocyte necrosis and fibrosis. The time of medication administration significantly impacts treatment outcomes. Hence this study evaluated the protective effect of time-modulated cimetidine (CT) against MTX-induced hepatotoxicity in albino rats. Methods: Thirty-six adult male albino rats were randomized into 6 groups. Group A (control) was injected intraperitoneally (IP) with normal saline (0.2 mL) for 24 h. Group B received CT (20 mg/kg IP) for 24 h. Group C was treated IP with MTX (20 mg/kg) for 24 h. Group C (pre-treatment) was injected IP with CT one hour before MTX administration for 24 h. Group E (co-treatment group) was co-treated IP with CT and MTX for 24 h. Group F (post-treatment group) was treated IP with one dose of MTX one hour before CT injection for 24 h. After treatments, the rats were weighed and euthanized. Blood samples were collected and their blood samples were evaluated for serum liver function markers, also liver samples were excised and used for biochemical and histological studies. Results: The liver of MTX-treated rats was characterized by hepatocyte necrosis. Aminotransferases, gamma-glutamyl transferase, lactate dehydrogenase, alkaline phosphatase, conjugated bilirubin, total bilirubin, and malondialdehyde activities were significantly (P<0.001) up-regulated in MTX-treated rats. However, glutathione, catalase, superoxide dismutase, and glutathione peroxidase activities were significantly (P<0.001) down-regulated in MTX-treated rats. The above hepatotoxic changes were significantly attenuated in rats pre-treated (P<0.001), co-treated (P<0.01), and post-treated (P<0.05) with CT when compared to MTX group.  Conclusion: However, pre-treatment with CT was most effective, hence it may be clinically useful for MTX-induced hepatotoxicity. 


Author(s):  
KELVIN THEANDRO GOTAMA ◽  
VIVIAN SOETIKNO ◽  
MELVA LOUISA ◽  
WAWAIMULI AROZAL

Objective: The antineoplastic agent doxorubicin (DOX) is known for causing liver toxicity. Its metabolism in hepatocytes causes oxidative stress, which,in turn, induces DNA damage, lipid peroxidation, ATP depletion, and apoptosis. L-citrulline (CIT), a commonly found agent in fruits like watermelon,has piqued interest due to its antioxidant properties. In the body, CIT is converted to nitric oxide, which has been shown to mitigate hepatic injuryby scavenging free radicals, improving hepatic sinusoidal microcirculation, and inhibiting neutrophilic infiltration. This study aims to investigate CITability to prevent DOX-induced hepatotoxicity.Methods: A total of 20 Wistar rats were randomized to receive either DOX (10 mg/kg BW) or NaCl 0.9%. DOX-intoxicated group was further randomizedto either received low-dose CIT (300 mg/kg BW), high-dose CIT (600 mg/kg BW), or aquadest. CIT was given orally for 6 days and DOX throughintraperitoneal injection on days 4 and 5. Serum was obtained and hepatotoxicity was assessed with serum levels of aspartate aminotransferase(AST), alanine aminotransferase (ALT), and gamma-glutamyl transferase (GGT). Statistical analysis was done with one-way ANOVA and Tukey’s test.Results: Serum ALT, AST, and GGT were increased significantly compared to that of normal group. CIT administration in both the doses could decreasethe serum levels of ALT and AST significantly compared to that of DOX group. In this study, CIT in both the doses could reduce the serum levels of GGTcompared to that of DOX group though not statistically significant.Conclusions: This study suggests that CIT exerts hepatoprotective effect, as evident by the attenuation of serum biomarkers.


Author(s):  
Elias Adikwu ◽  
Udeme Owunari Georgewill

Artemether/lumefantrine/tinidazole (A/L/T) has shown additive antiplasmodial activity; therefore its safety assessment is imperative. This study examined its hepatotoxic effect on healthy and diseased mice. Fifty four Swiss albino mice of n=6 were used. The mice were diseased with Plasmodium berghei ( ) and treated with T (28.6 mg/kg), A/L (2.3/13.7mg/kg) and A/L/T for 4 days, respectively. Healthy mice were treated with T (28.6 mg/kg), A/L (2.3/13.7mg/kg) and A/L/T for 28 days, respectively. After drug treatment; the mice were weighed and anesthetized. Liver samples were excised, weighed and evaluated for oxidative stress indices and histology. Blood samples were assessed for serum liver function indices. Treatment with T, A/L and A/L/T produced no significant (p>0.05) effects on all evaluated parameters in parasitized mice when compared to control. Significant decrease in body weight with significant increase in liver weight occurred in healthy mice treated with A/L (p<0.05) and A/L/T (p<0.01) when compared to control. Impaired liver function  characterized by significantly increased serum aminotranferases, alkaline phosphatase, lactate dehydrogenase, gamma-glutamyl transferase, and bilirubin levels with significantly decreased total protein and albumin levels occurred in healthy mice treated with T (p<0.05), A/L (p<0.01) and A/L/T (p<0.001) when compared to control. Significantly decreased glutathione peroxidase, superoxide dismutase, glutathione, and catalase levels with significantly increased malondialdehyde levels occurred in healthy mice treated with T (p<0.05), A/L (p<0.01) and A/L/T (p<0.001) when compared to control. A/L/T caused hepatocyte necrosis in healthy mice. The use of A/L/T for malaria treatment seems safe on the liver, but may impair liver function with prolonged use. 


2022 ◽  
Vol 52 (6) ◽  
Author(s):  
Renata Barcelos Repoles ◽  
Clarice Silva Cesario ◽  
Edilberto Nobrega Martinez ◽  
Waldomiro de Paula Lopes ◽  
Delma Henriques Rodrigues ◽  
...  

ABSTRACT: The coati (Nasua nasua, Linnaeus 1766) is a generalist species, feeding on often-discarded human food in dumpsters around ecological tourism sites. We investigated the body weight and some blood chemistry variables related to the diet of wild coatis from three parks: Parque Municipal das Mangabeiras (PM), Parque Nacional do Caparaó (PNC) e Estação Ecológica Água Limpa (EEAL). We tested the plasma of 53 coatis for high-density lipoprotein (HDL), alanine transaminase (ALT), aspartate transaminase (AST), gamma-glutamyl transferase (GGT), cholesterol (Chol), triglycerides (Trig), and alkaline phosphatase (ALP). Male and female adults did not significantly differ on the weight (P > 0.05) and blood chemistry indexes (P > 0.05). The adult coatis of the PM were heavier than the adult coatis of the other two parks. There were significant differences in HDL (P < 0.04), AST (P < 0.001), ALT (P < 0.001), and GGT (P < 0.001) between adults of the three parks. Only ALT and ALP were significantly different (P < 0.05) among the young coatis. The results suggested the coatis of the three parks have different health status. The consumption of discarded human food seems to affect body weight of the PM coatis. The coatis from PNC and EEAL had blood chemistry profiles suggestive of liver disorder. We recommend carrying on environmental education programs to visitors and additional clinical investigations on coatis from these parks.


Author(s):  
Eman Aly Sadeek Fadlalla ◽  
Sahar Mousa Galal

Background: Paracetamol overdose is a predominant cause of hepatotoxicity and nephrotoxicity in both humans and experimental animals. There is an emerging focus on plant products to find a highly effective and reliable drug for the prevention of paracetamol –induced toxicity. Objective: In this study, we investigated the Hepatoprotective and Reno-protective Effects of artichoke (Cynara scolymus L.) Leaf extract and rosemary (Rosmarinus officinalis L.) extract against paracetamol Induced toxicity in Albino Rats. Materials and Methods: Rats were divided into five groups: Negative control, paracetamol (1000 mg/kg dose) PCT, artichoke leaf extract “ALE” (1.5  g/kg, orally + paracetamol for 30 d), rosemary extract “RE” (125  mg/kg + paracetamol for 30 days) and the last group was treated with PCT+ ALE+ RE for 30 days. Results: Paracetamol caused marked liver damage as noted by significant increased activities of serum aminotransferases, alkaline phosphatase, gamma-glutamyl transferase and lactate dehydrogenase. Paracetamol also raised serum levels of urea, creatinine, and Cystatin-C. In addition, there was a significant decrease in serum total protein and albumin. Paracetamol caused an elevation in lipid peroxidation paralleled with significant decline in reduced glutathione (GSH) level and activities of glutathione-S- transferase (GST), glutathione (GPX) peroxidase, and superoxide dismutase (SOD) in the liver and kidney. These results are confirmed in the histological examination of the liver and kidney. Conclusion: Treatment with artichoke leaf extract (ALE) and rosemary extract (RE) produced a potential protection of the liver and kidney against biochemical and histological alterations and oxidative stress induced by paracetamol.


Author(s):  
T. T. El-Sisy ◽  
Asmaa A. Salem ◽  
Nivin S. Nail ◽  
Jehan B. Ali

Aflatoxins (AFs) are dangerous mycotoxins, which include a great number of lipophilic molecules produced by aerobic microscopic fungi belonging to the genus Aspergillus causes health hazard including death to human and livestock. The objective of this study was to evaluate the effectiveness of ozone gas treatment on the fungal growth and detoxification of AFs - contaminated wheat and corn grains. Ozone concentration treatments 40 mg / Kg wheat for 1 hour and 80 mg / Kg corn for 2 hours of exposure time respectively were applied to contaminated samples of wheat and corn grains. It was observed that completely inhibition of Aspergillus growth and consequently the total aflatoxin content was decreased. In vivo, the biosafety assessment for 72 male albino rats fed on diet containing 70% wt. of ozone treated AFs – contaminated grains were evaluated comparing to control groups. Results indicated that rats fed on AFs contaminated grains have significantly increased the serum enzymes activity of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), gamma glutamyl transferase (GGT), malondialdehyde (MDA) content as well as the serum levels of creatinine, urea, glucose, total cholesterol (TC) and triglycerides (TG). Also, it was observed that a significant decrease in the level of serum total protein (TP), albumin (Alb), reduced glutathione (GSH) and testosterone hormone comparing to control groups.  However, the oral administration of ozonized groups ameliorated the biochemical parameters compared to rats fed on contaminated grains. Moreover, histopathological studies of liver, kidney and testis tissues of rats fed on contaminated grains that revealed different lesions and changes in tissues, inversely to that improving effects in tissues of ozonized contaminated grains – fed rats. It was concluded that ozonization treatment were most effective in reduction of mold count and degradation of aflatoxins content for grains during storage.


2019 ◽  
Vol 8 (2) ◽  
pp. 47-52
Author(s):  
Elias Adikwu ◽  
James Kemelayefa ◽  
Winifred Ocheiga

Medication use during pregnancy is challenging due to the occurrence of maternal or fetal toxicities. Atazanavir/ritonavir (ATV/r) has hepatotoxic potential hence; use in pregnant patients living with human immunodeficiency virus may cause maternal hepatotoxicity. This study assessed the liver profile of ATV/r in pregnant albino rats. Thirty pregnant albino rats randomized into groups were orally treated daily with ATV/r (4.28/1.43 mg/kg-34.3/11.4 mg/kg) for 16 days. After treatment, the rats were weighed and sacrificed. Blood samples were collected and examined for serum biochemical parameters. Liver samples were weighed and assessed for biochemical and histological changes. Body and liver weights were normal (p>0.05) in ATV/r-treated pregnant rats when compared to control. Serum total cholesterol, triglyceride, low density lipoprotein cholesterol and blood glucose levels were significantly (p<0.01) elevated whereas high density lipoprotein cholesterol level was significantly (p<0.01) decreased in rats treated with ATV/r (34.3/11.4 mg/kg) when compared to control. Liver and serum aminotransferases, alkaline phosphatase, gamma-glutamyl transferase, lactate dehydrogenase, total bilirubin, and conjugated bilirubin levels were significantly increased in a dose-dependent fashion in rats treated with ATV/r; 8.57/2.86 mg/kg (p<0.05), 17.1/5.72 mg/kg (p<0.01) and 34.3/11.4 mg/kg (p<0.001) when compared to control. Liver superoxide dismutase, catalase, glutathione and glutathione peroxidase levels were significantly decreased whereas malondialdehyde levels were significantly increased in a dose-dependent fashion in rats treated with ATV/r; 8.57/2.86 mg/kg (p<0.05), 17.1/5.72 mg/kg (p<0.01) and 34.3/11.4 mg/kg (p<0.001) when compared to control. Necrotic hepatocytes were observed at higher doses of ATV/r. ATV/r may not be hepatotoxic in pregnant women living with HIV at the clinical dose.


2019 ◽  
Vol 43 (1) ◽  
Author(s):  
Manal G. Mahmoud ◽  
Mohsen S. Asker ◽  
Mohamed E. El Awady ◽  
Amal I. Hassan ◽  
Nadia A. R. Zaharan ◽  
...  

Abstract Background Nanomedicine contributes to the efficiency of pharmacological treatments and progresses rapidly. The present study was designed to produce exopolysaccharide (BSEPS) from Bacillus subtilis sp. strain reported in our previous study was further characterized, and its BSEPS for synthesis of the nanoparticle Ag-BSEPS using microwave heating to determine the possible effects of a prepared solution containing Ag-BSEPS versus thioacetamide (TAA) evoked liver fibrosis in Wister albino rats. Nanoparticles with silver (Ag) core have been synthesized in an aqueous solution after exposure of BSEPS to periodate oxidation. Animals were split into four groups: I - control rats, water ad libitum for 6 weeks; II - rats were injected with TAA 200 mg/kg-1 3 times/week for 4 weeks IP; III - Ag-BSEPS 100 mg/kg-1 IP twice a week for 6 weeks; and IV - TAA, as group II followed by Ag-BSEPS as group III. The antifibrotic effects of Ag-BSEPS were appraised by determining different hepatotoxicity indices, oxidative stress, and inflammatory and liver fibrosis markers. Results Nanoparticles were obtained with a diameter size range of 50–100 nm characterized by SEM and TEM without using any harmful reagents. Results evinced considerably reduced activity of liver functions such as transaminases (AST, ALT), gamma-glutamyl transferase (GGT), and alkaline phosphatase (ALP) in the group which received TAA followed by Ag-BSEPS compared to the other group which received only TAA. In the current results, the administration of Ag-BSEPS showed an improvement in the proinflammatory cytokines. On the contrary, the antioxidant enzymes in liver homogenates revealed significant improvement (concentration of glutathione peroxidase (GSH-PX), superoxide dismutase (SOD), and catalase (CAT) increases) in animals with TAA-induced liver damage followed by Ag-BSEPS. Moreover, the activities of the fibrotic markers transforming growth factor-beta 1(TGF-β1) and type III pro-collagen (PCIII) were increased in liver tissues in the group which was given TAA alone as compared to the controls. The percentage of fibrosis of hepatic tissue had a positive correlation with the levels of PCIII and TGF-β1, followed by Ag-BSEPS compared to the TAA group without nanocomposite treatment. Microscopic examinations revealed inhibitory effects of Ag-BSEPS on inflammatory changes and deterrent of liver fibrosis. Conclusion It was suggested that the biochemical and histological amelioration observed in Ag-BSEPS (100 mg/kg-1 twice a week for 6 weeks) treated the fibrotic rats.


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