Protective role of thymoquinone against liver damage induced by tamoxifen in female rats

2014 ◽  
Vol 92 (8) ◽  
pp. 640-644 ◽  
Author(s):  
Ghada M. Suddek

One of the major reasons for terminating a clinical trial is the liver toxicity induced by chemotherapy. Tamoxifen (TAM) is an anti-estrogen used in the treatment and prevention of hormone-dependent breast cancer. Tamoxifen therapy may cause hepatic injury. The seeds of Nigella sativa, which contain the active ingredient thymoquinone (TQ), have been used in folk medicine for diverse ailments. TQ is reported to possess anticancer and hepatoprotective effects. In this study, the protective effects of TQ against TAM-induced hepatotoxicity in female rats were evaluated. Four groups of rats were used: control; TAM; TQ; TAM+TQ. TAM (45 mg·(kg body mass)–1·day–1, by intraperitoneal injection (i.p.), for 10 consecutive days) resulted in elevated serum levels of alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, lactate dehydrogenase, total bilirubin, and gamma glutamyl transferase, as well as depletion of reduced glutathione in the liver and accumulation of lipid peroxides. Also, TAM treatment inhibited the hepatic activity of superoxide dismutase. Further, it raised the levels of tumor necrosis factor alpha in the liver and induced histopathological changes. Pretreatment with TQ (50 mg·(kg body mass)–1·day–1; orally, for 20 consecutive days, starting 10 days before TAM injection) significantly prevented the elevation in serum activity of the assessed enzymes. TQ significantly inhibited TAM-induced hepatic GSH depletion and LPO accumulation. Consistently, TQ normalized the activity of SOD, inhibited the rise in TNF-α and ameliorated the histopathological changes. In conclusion, TQ protects against TAM-induced hepatotoxicity.

2008 ◽  
Vol 27 (11) ◽  
pp. 837-843 ◽  
Author(s):  
V Maphosa ◽  
PJ Masika ◽  
AA Adedapo

The aqueous extract from Leonotis leonurus (L) R.Br. (Lamiaceae) shoots was evaluated in female rats for its acute, sub acute, and chronic toxicity together with hematological, biochemical, and histopathological changes. In the acute toxicity test, the extract caused death in animals receiving 3200 mg/kg dose. The extract also caused significant ( P < 0.05) changes in red blood cells, packed cell volume, hemoglobin concentration, mean corpuscular volume, platelets, white blood cells and its differentials at doses of 1600 mg/kg in sub-acute toxicity and in as low as 200 mg/kg in chronic toxicity. In biochemical parameters, the extract caused a significant ( P < 0.05) decrease in the levels of urea and creatinine at 1600 mg/kg dose and a significant ( P < 0.05) reduction in urea, total bilirubin, total protein, albumin, globulin, glutamine transference gamma-glutamyl transferase (GGT), and alanine transminase in the 400 mg/kg dose in chronic toxicity. Changes were also noted in body weights, but no significant changes were observed in the levels of electrolytes (sodium, potassium, and chloride). Clinico-pathologically, starry hair coat, respiratory distress, and mortality were recorded. The extract also caused various histopathological changes in the organs. The study concluded that farmers need to exercise caution in the use of the plant for medicinal purposes.


2014 ◽  
Vol 92 (11) ◽  
pp. 965-973 ◽  
Author(s):  
Dalia O. Saleh ◽  
Gehad A. Raheem Abdel Jaleel ◽  
Sally A. El-Awdan ◽  
Fatma Oraby ◽  
Manal Badawi

This study aimed to investigate the possible protective effects of genistein (GEN), a phytoestrogen, on the liver injury induced in rats by thioacetamide (TTA; 200.0 mg·(kg body mass)–1; administered 3 times a week by intraperitoneal injection). GEN (0.5, 1.0, or 2.0 mg·(kg body mass)–1; by subcutaneous injection) was concurrently administered on a daily basis for 8 weeks, and its effects were evaluated 24 h after the administration of the last dose. The results from this study revealed that TTA-induced liver injury was associated with massive changes in the serum levels of liver biomarkers, oxidative stress markers, and liver inflammatory cytokines. Treatment of TAA-induced liver injury in rats with GEN decreased the elevated serum levels of aspartate aminotransferase, alanine aminotransferase, and total and direct bilirubin, and increased the serum level of albumin. GEN also restored the liver levels of malondialdehyde and reduced glutathione, as well as tumor necrosis factor-alpha, interleukin-6, and their modulator nuclear factor kappa-light-chain-enhancer of activated B cells. From our results, it can be concluded that GEN attenuates the liver injury-induced in rats with TAA, and this hepatoprotective role is attributed to its anti-inflammatory and antioxidant properties.


2018 ◽  
Vol 2018 ◽  
pp. 1-11 ◽  
Author(s):  
Tarfa Albrahim ◽  
Manal Abdulaziz Binobead

It is common for food to be made more palatable through the use of the flavour enhancer monosodium glutamate, also known as vetsin powder. The purpose of the study described in this paper was to explore how vetsin-induced hepatic toxicity, DNA fragmentation, damage, and oxidative stress modifications could be mitigated with moringa leaf extract (MLE). To that end, 40 male rats were separated into four groups: normal control, positive control or MLE, vetsin, and vetsin combined with MLE. Results indicated that, compared to the control group, the levels of serum alanine aminotransferase (ALT), aminotransferase (AST), alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT), liver malondialdehyde (MDA), DNA damage, injury, PCNA, and P53 expressions were significantly enhanced by the administration of vetsin (P<0.05). However, the vetsin group had significantly reduced levels of albumin, globulin, total protein, liver glutathione (GSH), superoxide dismutase enzyme (SOD), catalase, and glutathione S-transferase (GST) enzyme activities (P<0.05) by comparison to control. Meanwhile, modifications in liver functions, oxidative stress, DNA damage, liver injury, and PCNA expression were alleviated when vetsin was administered alongside MLE. The authors conclude that vetsin may have many side effects and that MLE can ameliorate biochemical changes, oxidative stress, hepatic injury, PCNA, and P53 alterations induced by vetsin administration.


2020 ◽  
Vol 39 (12) ◽  
pp. 1585-1595
Author(s):  
AM Emara ◽  
KA Alrasheedi ◽  
MA Aldubayan ◽  
AH Alhowail ◽  
RM Elgarabawy

A significant health risk exists within a section of health workers that are exposed to anaesthetic gas and vapours, found in the atmosphere of treatment or operating rooms. These compounds are classified as waste anaesthetic gases (WAG). The present study aimed at identifying alterations in hepatic and haematological parameters occurring as a result of chronic exposure to WAG potentially affecting the health of team members working in hospitals. Therefore, operating room operatives, vulnerable to long-standing WAG exposure, were recruited for this study. Sevoflurane anaesthesia metabolites (inorganic fluoride and hexafluoroisopropanol (HFIP)), haematological indices and liver toxicity markers (alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, gamma-glutamyl transferase and osteopontin) were measured. The collected results showed increased plasma inorganic fluoride, HFIP and liver toxicity markers, as well as disturbances in haematological parameters. In conclusion, exposure to halogenated inhalational anaesthetics, in general, and Sevoflurane, in particular, induces alterations in hepatic markers and haematological indices.


2003 ◽  
Vol 40 (3) ◽  
pp. 317-327 ◽  
Author(s):  
H. Wisløff ◽  
A. Flåøyen ◽  
N. Ottesen ◽  
T. Hovig

We studied the effects of Narthecium ossifragum on goat kidneys. Twenty-five Norwegian dairy goats, 5 weeks to 4 months of age, were orally dosed with an aqueous extract from N. ossifragum. In experiment 1, we studied microscopic and functional changes in 12 animals that were euthanatized 2, 3, 4, 5, and 6 days after treatment. In experiment 2, we included ultrastructural studies on serial renal biopsies and urine analysis from five extract-treated animals and two controls. In addition, urine samples were collected from four dosed and two control goats. Ultrasonography revealed perirenal and retroperitoneal fluids. Microscopic changes were observed after 6 hours. The findings, most obvious in the inner cortex and the outer medulla, consisted of cytoplasmic vacuolization, interstitial edema, and focal necrosis of tubular epithelial cells. Ultrastructurally, the tubules had loss of microvilli, irregular cytoplasmic vacuolization, mitochondrial swelling with loss of cristae, and irregular but continuous basement membranes even with necrosis. In the glomeruli, there were occasional endothelial damage and shortening and swelling of the foot processes. Peritubular capillaries had breaks in the vessel walls and irregular endothelial cell edema, and the interstitium had marked edema. The functional lesions included elevated serum urea, creatinine, and magnesium concentrations, a slight decrease in serum calcium concentration, elevated urine protein and urine protein-creatinine ratio, and increased activities of urine alkaline phosphatase and gamma glutamyl transferase. Our findings indicate a fast-acting toxic principle inducing damage by both direct toxic and secondary ischemic effects.


Author(s):  
Ahmet Yozgat ◽  
benan kasapoglu ◽  
Alpaslan Tanoğlu ◽  
Güray Can ◽  
Yusuf Serdar Sakin ◽  
...  

Aim: In this study, we aimed to define the predictive role of liver function tests at admission to the hospital in outcomes of hospitalized patients with COVID-19. Material and Method: In this multicentric retrospective study, a total of 269 adult patients (≥18 years of age) with confirmed COVID-19 who were hospitalized for the treatment were enrolled. Demographic features, complete medical history, and laboratory findings of the study participants at admission were obtained from the medical records. Patients were grouped regarding their ICU requirements during their hospitalization periods. Results: Among all 269 participants, 106 were hospitalized in the intensive care unit (ICU) and 66 died. The patients hospitalized in ICU were older than patients hospitalized in wards (p=0.001) and expired patients were older than alive patients (p=0.001). Age, elevated serum D-dimer, creatinine, and gamma-glutamyl transferase (GGT) levels at admission were independent factors predicting ICU hospitalization and mortality in COVID-19 patients. Conclusion: In conclusion, in hospitalized patients with COVID-19, laboratory data on admission, including serum, creatinine, GGT and d-dimer levels have an important predictive role for the ICU requirement and mortality. Since these tests are readily available in all hospitals and inexpensive, some predictive formulas may be calculated with these parameters at admission, to define the patients requiring intensive care.


2001 ◽  
Vol 69 (9) ◽  
pp. 5352-5362 ◽  
Author(s):  
Matthias Eberl ◽  
Jan A. M. Langermans ◽  
Patrice A. Frost ◽  
Richard A. Vervenne ◽  
Govert J. van Dam ◽  
...  

ABSTRACT The radiation-attenuated Schistosoma mansoni vaccine is highly effective in rodents and primates but has never been tested in humans, primarily for safety reasons. To strengthen its status as a paradigm for a human recombinant antigen vaccine, we have undertaken a small-scale vaccination and challenge experiment in chimpanzees (Pan troglodytes). Immunological, clinical, and parasitological parameters were measured in three animals after multiple vaccinations, together with three controls, during the acute and chronic stages of challenge infection up to chemotherapeutic cure. Vaccination induced a strong in vitro proliferative response and early gamma interferon production, but type 2 cytokines were dominant by the time of challenge. The controls showed little response to challenge infection before the acute stage of the disease, initiated by egg deposition. In contrast, the responses of vaccinated animals were muted throughout the challenge period. Vaccination also induced parasite-specific immunoglobulin M (IgM) and IgG, which reached high levels at the time of challenge, while in control animals levels did not rise markedly before egg deposition. The protective effects of vaccination were manifested as an amelioration of acute disease and overall morbidity, revealed by differences in gamma-glutamyl transferase level, leukocytosis, eosinophilia, and hematocrit. Moreover, vaccinated chimpanzees had a 46% lower level of circulating cathodic antigen and a 38% reduction in fecal egg output, compared to controls, during the chronic phase of infection.


2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
Naveen T. Krishnareddy ◽  
Jestin V. Thomas ◽  
Saritha S. Nair ◽  
Johannah N. Mulakal ◽  
Balu P. Maliakel ◽  
...  

Considering the recent interest in free (unconjugated) curcuminoids delivery, the present study investigated the efficacy of a novel food-grade free-curcuminoids delivery system (curcumin-galactomannoside complex; CGM) in improving the hepatic function markers (inflammation and oxidative stress) in chronic alcoholics. The double-blinded, placebo-controlled study randomized 48 subjects with elevated serum transaminases and gamma-glutamyl transferase (GGT) levels, who were allocated to two groups (n=24) and to receive either placebo or CGM at (250 mg × 2)/day for 8 weeks. While liver function markers (transaminases and GGT) in the placebo group showed an increase (~ 9.5%), CGM group indicated a significant decrease in transaminases (31%) and GGT (29%) from the baseline levels. The beneficial effect of CGM was also clear from the significant increase (p <0.001) in endogenous antioxidants (GSH, SOD, and GPx) and decrease in inflammatory markers (IL-6 and CRP) levels (p <0.001) as compared to both the baseline and placebo group. To summarize, the nutritional intervention of CGM-curcumin was found to offer a significant hepatoprotective effect to attenuate the alcohol induced alterations to hepatic function markers. The Indian Medical Council and Drug Controller General of India approved Clinical Trial Registry No. CTRI/2018/03/012385.


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