scholarly journals Zingerone Attenuates Methotrexate-Induced Hepatotoxicity in Rats

2021 ◽  
Vol In Press (In Press) ◽  
Author(s):  
Mehdi Goudarzi ◽  
Zahra Basir ◽  
Alireza Malayeri ◽  
Ali Nesari ◽  
Narjes Zaeemzadeh

Background: Methotrexate (MTX) is mainly used for the chemotherapy of different types of malignancy and some autoimmune diseases like rheumatoid arthritis and inflammatory bowel disease. The MTX application is limited by its severe side effects, including several types of hepatic injury. Objectives: In this study, we decided to evaluate if zingerone (the main constituent of ginger) can reduce the hepatic side effects of MTX. Methods: Thirty-five rats were divided into five groups: Control group receiving normal saline (N/S), once daily, by gavage, for 10 days, and N/S intraperitoneally (i.p.), a single dose on the ninth day; Methotrexate (MTX) group receiving N/S, once daily, by gavage, for 10 days, and MTX (i.p.), a single dose (20 mg/kg) on the ninth day; Groups 3 (ZG25), 4 (ZG50), and 5 (ZG100) receiving zingerone (25, 50, and 100 mg/kg, respectively), once daily, by gavage, for 10 days, and MTX (i.p.), a single dose (20 mg/kg) on the ninth day. Results: The results showed a significant decrease in serum AST, ALT, and ALP, as well as the hepatic content of MDA, NO, PC, TNF-α, and IL-1β, in the ZG groups compared with the MTX group. The activity of SOD, CAT, and GPX, as well as the hepatic content of GSH, showed a significant increase in the ZG groups compared with the MTX group. Histopathological improvement in the hepatic tissue of ZG groups compared with the MTX group confirmed all other findings. Conclusions: It is concluded that zingerone can improve hepatic injury induced by MTX in rats regarding the redox system features, inflammation, and histological changes. This can make humans hopeful for using Ginger in the future for attenuating the hepatic side effects of MTX when used chronically.

2020 ◽  
Vol 63 (1) ◽  
Author(s):  
Guili Bao ◽  
Yinglong Zhang ◽  
Xiaoguang Yang

AbstractIn this study, lemon peel flavonoids (LPF) were administered to investigate its effect on the anti-fatigue and antioxidant capacity of mice that undergo exercise until exhaustion. LPF (88.36 min in LPFH group mice) significantly increased the exhaustion swimming time compare to the untreated mice (40.36 min), increased the liver glycogen and free fatty acid content in mice and reduce lactic acid and BUN content in a dose-dependent manner. As the concentration of lemon peel flavonoids increased, the serum creatine kinase, aspartate aminotransferase, and alanine aminotransferase levels of mice gradually decreased. LPF increases superoxide dismutase (SOD) and catalase (CAT) levels in mice and reduces malondialdehyde levels in a dose-dependent manner. And LPF raises hepatic tissue SOD, CAT activities and reduces skeletal muscle tissue iNOS, TNF-α levels of mice compared to the control group. LPF also enhanced the expression of copper/zinc-superoxide dismutase (Cu/Zn-SOD), manganese-superoxide dismutase (Mn-SOD), and CAT mRNA in mouse liver tissue. LPF also enhanced the expression of alanine/serine/cysteine/threonine transporter 1 (ASCT1) mRNA and attenuate the expression of syncytin-1, inducible nitric oxide synthase (iNOS), and tumor necrosis factor (TNF)-α in mouse skeletal muscle. According to high-performance liquid chromatography (HPLC) analysis, it was found that LPF contains flavonoids such as rutin, astragalin, isomangiferin, naringin, and quercetin. Our experimental data show that LPF has good anti-fatigue effects and anti-oxidation ability. In summary, LPF has high prospects to be developed and added to nutritional supplements.


2016 ◽  
Vol 51 (2) ◽  
pp. 124-137
Author(s):  
Sergi Barrera-Ochoa ◽  
Irene Gallardo-Calero ◽  
Andrea Sallent ◽  
Alba López-Fernández ◽  
Ramona Vergés ◽  
...  

The aim is to create a new and safe experimental model of radiation-induced neurovascular histological changes with reduced morbidity and mortality for use with experimental microsurgical techniques. Seventy-two Sprague–Dawley rats (250–300 g) were divided as follows: Group I: control group, 24 rats clinically evaluated during six weeks; Group II: evaluation of acute side-effects (two-week follow-up period), 24 irradiated (20 Gy) rats; and Group III: evaluation of subacute side-effects (six-week follow-up period), 24 irradiated (20 Gy) rats. Variables included clinical assessments, weight, vascular permeability (arterial and venous), mortality and histological studies. No significant differences were observed between groups with respect to the variables studied. Significant differences were observed between groups I vs II–III regarding survival rates and histological changes to arteries, veins and nerves. Rat body weights showed progressive increases in all groups, and the mortality rate of the present model is 10.4% compared with 30–40% in the previous models. In conclusion, the designed model induces selective changes by radiotherapy in the neurovascular bundle without histological changes affecting the surrounding tissues. This model allows therapeutic experimental studies to be conducted, including the viability of microvascular and microneural sutures post radiotherapy in the cervical neurovascular bundle.


2008 ◽  
Vol 62 (3) ◽  
pp. 191-196 ◽  
Author(s):  
Biljana Govedarica ◽  
Vukosava Djordjevic-Milic ◽  
Natasa Radic ◽  
Branislava Srdjenovic ◽  
Aleksandar Djordjevic

The antracycline antibiotics have one of the widest areas of use in oncology. The most investigated mechanisms of their antineoplastic activity include: interactions of these antibiotics with DNA, inhibition of topoisomerase II and production of free radicals. However, the side effects of doxorubicin, especially cardiotoxicity, are the limiting factor of its use in cancer therapy. The aim of this research was to investigate the influence of fullerenol ?60(?H)24 as a cytoprotector in single doze administration of doxorubicin on the activity of enzymes in serum (CK, AST, ALT, LDH and a-HBDH) in rats in in vivo system. Activity of enzymes (CK, LDH, HBDH, AST, and ALT) in serume was measured with standard commercial methods. The results of analysis of the samples treated with the combination of fullerenol and doxorubicin show no difference in enzyme activity in comparison with the control group. The results indicate the possibility of using fullerenol as a protector in the therapy with doxorubicin in malign neoplasm.


2019 ◽  
Vol 50 (4) ◽  
pp. 386-396 ◽  
Author(s):  
Johannes P.D. Schultheiss ◽  
Eelco C. Brand ◽  
Evert Lamers ◽  
Willemijn C.M. van den Berg ◽  
Fiona D.M. van Schaik ◽  
...  

2001 ◽  
Vol 46 (No. 6) ◽  
pp. 153-159 ◽  
Author(s):  
I. Herzig ◽  
B. Písaříková ◽  
I. Diblíková ◽  
P. Suchý

Experimental groups of pigs were treated orally with 120 mg (Group O 120), or 480 mg (Group O 480) of iodine per animal, or intramuscularly with 240 mg (Group I 240) of iodine per animal. Iodine was administered in the form of iodised fatty acid esters (IFAE). The treatment resulted in significantly increased iodine concentrations in tissues and a single dose was sufficient to meet the requirement for the whole fattening period (180 days). Urinary iodine concentrations in all the experimental groups were higher than in the control group C receiving iodine only from conventional feed. Urinary excretion of iodine between days 2 and 5 was more distinctive in orally treated than in intramuscularly treated animals (Figure 1). Iodine concentrations at the end of the fattening period (day 180) were higher in the treated than in the control groups. The treatment effect was more marked in Groups O 480 and I 240 than in Group O 120. The dynamics of blood serum iodine concentrations was similar to urinary concentrations (Figure 2). Mean thyroid gland weights in the groups O 120, O 480, I 240, and C were 9.19, 8.51, 7.10, and 12.01 g, respectively. An opposite tendency was observed for iodine concentrations in thyroid gland dry matter (Figure 3). No effects of any of the treatments on total protein, albumin, total lipids, or cholesterol concentrations in blood serum were observed. Group C showed lower tissue iodine concentrations than any of the experimental groups. The only exception was hepatic tissue in which approximately the same iodine concentrations were found in all the groups. Data obtained in Groups O 120, O 480, and I 240 indicate that decisive for tissue concentrations was rather the dose of iodine than the route of administration. Iodine is stored above all in the thyroid gland and adipose tissue. As can be seen in Figure 4, its concentration was higher in muscles with a higher proportion of fat (neck) than in lean muscles (ham).


Author(s):  
Sulaiman Yusuf ◽  
Yati Soenarto ◽  
Muhammad Juffrie ◽  
Wiryatun Lestariana

Background and Objectives: Inflammation in the intestine causes diarrhea due to an increased release of pro-inflammatory cytokines such as TNF-α, IL-1, and IL-6. These are triggered by the exposure of E. coli-LPS to epithelial cells of the intestinal mucosa as well as low concentration of zinc in plasma such as in infants or children who are experiencing diarrhea. This paper aims to determine the effects of zinc supplementation on pro-inflammatory cytokines (TNF-α, IL-1 and IL-6) in mice with E. coli-LPS-induced diarrhea. Materials and Methods: This study used a controlled trial experimental design in the laboratory. A sample size of 20 mice were randomly divided into 4 groups: 1) Control group was given standard foods, 2) Trial group was given E. coli-LPS 2.5 mg/kg/oral once on day1, 3) Prevention group was given E. coli-LPS + 30 mg/kg/oral of zinc once daily for 12 days, 4) Therapeutic group was given E. coli-LPS, and were then given 30 mg/kg/oral of zinc once daily for 12 days if diarrhea occurred. Blood samples of mice were taken through the orbital sinus on the 0, 5th, 10th hour, and on the 4th, 8th and 12th days. Results: Positive effects of zinc supplementation on levels of pro-inflammatory cytokines were observed, in which the higher levels of zinc were present, the lower levels of pro-inflammatory cytokines, especially TNF-α were observed. However, there was an increase of IL-1 and IL-6 levels on the 8th day in the prevention and therapeutic groups. Conclusion: Oral zinc supplementation had a significant positive effect on the levels of pro-inflammatory cytokines. Where there were higher levels of zinc, lower levels of pro-inflammatory cytokines TNF-α were present.


2017 ◽  
Vol 104 (2) ◽  
pp. 139-149 ◽  
Author(s):  
M Savran ◽  
E Cicek ◽  
DK Doguc ◽  
H Asci ◽  
S Yesilot ◽  
...  

Like several other anticancer drugs, methotrexate (MTX) causes side effects, such as neuropathic pain, hepatotoxicity, and nephrotoxicity. Abnormal production of reactive oxygen species has been suspected in the pathophysiology of MTX-induced hepatorenal toxicity. Therefore, the aim of this study was to investigate the probable protective role of vitamin C (Vit C) on oxidative stress induced by MTX in the liver and kidney tissues of rats. A total of 32 rats were randomly and equally divided into four groups. The first group served as the control group. The second group received a single dose of 20 mg/kg of MTX intraperitoneally. To demonstrate our hypothesis, the third and the fourth groups received 250 mg/kg of Vit C for 3 days by oral gavage, with or without MTX treatment. At the end of the study, the liver and kidney tissues of the rats were collected and examined using histology. Both the tissues were assayed for malondialdehyde concentration and superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) activities. In hepatic and renal tissues, lipid peroxidation levels were increased, whereas SOD, CAT, and GSH-Px levels were decreased by MTX. All parameters, including CAT levels in hepatic tissue, were significantly restored after the administration of Vit C for 3 days. Similar to the biochemical findings, evidence of oxidative damage was examined in both types of tissues by histopathological examination. From the results of this study, we were able to observe that Vit C administration modulates the antioxidant redox system and reduces the renal and hepatic oxidative stress induced by MTX. Vit C can ameliorate the toxic effect of MTX in liver and kidney tissues of rat.


Author(s):  
Zaida Rahman

A randomized controlled trial was conducted in one unit of Gynecology and Obstetrics Dept. of a Govt. hospital by giving a single dose preoperative prophylactic antibiotic and the results were compared with a control group who received a conventional prophylactic regimen of antibiotic combination. A total of 60 samples were taken from the patients currently admitted and undergoing total abdominal hysterectomy in one unit of the Department of Obstetrics & Gynecology of a Govt. hospital for this trial and they were divided into two groups - 30 Cases and 30 Control. Case group were given a single dose cephradine 1 gm IV just before induction of anesthesia. Control group were given Inj. Ciprofloxacin 200 mg IV 12 hrsly plus inj. Metronidazol 500 mg 8 hrsly till oral feeding followed by oral tab. Ciprofloxacin 500 mg 12 hrsly plus tab. Metronidazol 400 mg 8 hrsly in the remaining days which was then practicing in that gynecology unit of the Govt. hospital. Variables measured for the trial were total cost and duration of antimicrobial therapy, rate of postoperative infection and side effects of antimicrobial therapy. While comparing the outcome between the case and control group, it was observed that both the duration and cost (P<0.001) and also the side effects (P<0.05) of antimicrobial therapy were significantly higher in control group than the case group (duration of antimicrobial therapy was 2.9± 0.88 days in case group and 8. 9±0.58 days in control group and cost of antimicrobial therapy was 113.06± 24.53 taka in case group and 957.376±32.05 taka in control group). But the rate of post operative infection which is the main objective of giving preoperative antibiotic prophylaxis, was significantly higher in case group than the control group (P<0.05). But this infection rate could be reduced if the sterilization procedure of the operation theatre and general conditions of the patients were improved. If these risk factors could be minimized, single dose preoperative prophylactic antibiotic could be effectively practiced in our country. DOI: 10.3329/bjpp.v22i1.3560 Bangladesh J Physiol Pharmacol 2006; 22(1/2) : 1-4


2018 ◽  
Vol 14 (2) ◽  
pp. e22-e29 ◽  
Author(s):  
Eun-Ju Choi ◽  
Wi-Young So

Background and Objective We aimed to examine the impact of high-intensity swimming exercise and inflammatory bowel disease (IBD) on IL-1β, TNF-α, and COX-2 gene expression in the small intestine and colon of mice. Material and Methods Forty male C57BL/6 mice were divided into 4 groups: the control group (CON), swimming exercise group (EX), 50% ethanol (EtoH) control group (50%EtoH CON), and 2,4,6-trinitrobenzene sulfonic acid group (TNBS). The EX group performed 4 weeks of exercise. Intrarectal TNBS injection induced IBD in the TNBS group; the 50%EtoH CON group received control injections. Reverse transcription and real-time polymerase chain reaction were used to examine IL-1β, TNF-α, and COX-2 mRNA expression in the small intestine and colon. Results IL-1β, TNF-α, and COX-2 mRNA expression was significantly increased in the EX group compared to that in the CON group (p’s<0.05). IL-1β and COX-2 mRNA expression was significantly increased in the TNBS group compared to that in the 50%EtoH CON group (p’s<0.05). Conclusion Thus, inflammatory cytokine IL-1β and COX-2 expression in the small intestine and colon was increased in both high-intensity swimming exercise and IBD models. However, TNF-α was increased only in the swimming exercise model. Further research is required to confirm these observations and establish swimming exercise regimes appropriate for patients with IBD.


2016 ◽  
Vol 19 (2;2) ◽  
pp. E319-E327 ◽  
Author(s):  
Eliana Marisa Ganem

Background: There is experimental evidence that dexmedetomidine has neuroprotective effects. So, it could be expected that its intrathecal or epidural administration presents no harm. However, whether dexmedetomidine is neurotoxic to the spinal cord remains to be fully elucidated. Objective: To evaluate the effect of preservative-free dexmedetomidine administered as a subarachnoid single injection on the spinal cord and meninges of rabbits. Study Design: Research article. Setting: Experimental research laboratory. Methods: Twenty young adult female rabbits, each weighing between 3200 and 4900 g, and having a spine length between 36 and 40 cm, were divided by lot into 2 groups (G): 0.9% saline in G1 and preservative-free dexmedetomidine in G2 (dose of 10 μg). After intravenous anesthesia with ketamine and xylazine, the subarachnoid space was punctured at S1-S2 under ultrasound guidance, and a random 5 µl.cm-1 of spinal length (0.2 mL) of solution (saline or dexmedetomidine) was injected. The animals remained in captivity for 21 days under medical observation and were sacrificed by decapitation. The lumbosacral spinal cord portion was removed for immunohistochemistry to assess the glial fibrillary acidic protein (GFAP), and histology was assessed using hematoxylin and eosin (HE) stain. Results: None of the animals had impaired motor function or decreased nociception during the period of clinical observation. None of the animals from the control group showed signs of injuries to meninges. In the dexmedetomidine group, however, 9 animals presented with signs of meningeal injury. The main histological changes observed were areas with meningeal thickening and lymphoplasmocitary infiltration in the pia-mater and arachnoid. Further histological examination also revealed adherence areas among the pia and arachnoid. There was no signal of injury in neural tissue in any animal of both groups. Limitations: Evaluation of the possible analgesic effects of the intrathecal dexmedetomidine was not performed. Conclusion: On the basis of the present results, dexmedetomidine administered in the subarachnoid space in a single dose of 10 µg is capable of producing histological changes over the meninges of rabbits. Key Words: Anesthesia, spinal; dexmedetomine; injections, spinal; spinal cord; rabbits


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