Hepatoprotective and antioxidant activity of N-acetyl cysteine in carbamazepine-administered rats

Maheswari, Eswaran; Saraswathy, Ganesan Raja Lekshmi; Thakur, Santhranii

doi:10.4103/0253-7613.129321

Cited by 26 publications

(14 citation statements)

References 28 publications

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“…The slightly increased plasma ALT levels in the CBZ-treated SD rats were considered to be related to the increased liver weights. These results were consistent with the results of the studies previously reported (Maheswari et al, 2014;Iida et al, 2015). On the other hand, in the CBZ-treated SDT fatty rats, slight necrosis was noted in the centrilobular hepatocytes and the plasma levels of ALT, GU and T-BIL were increased.…”

Section: Discussionsupporting

confidence: 93%

“…CBZ is metabolized by the hepatic CYP3A family. The main metabolic pathways of CBZ are epoxidation and hydroxylation, though conjugation reactions may also have a role (Maheswari et al, 2014;Bernus et al, 1996). 10,11-CBZ epoxide is the most important metabolic product of CBZ (Driefus and Langer, 1987).…”

Section: Discussionmentioning

confidence: 99%

“…The development of CBZ-induced hepatotoxicity is somehow related to disturbance of glutathione metabolism, although data in this regard are limited (Kalapos, 2002). CBZ is metabolized by the hepatic CYP3A family of microsomal enzymes and epoxidation and hydroxylation are the main metabolic pathways, though conjugation reactions may also play a role (Bernus et al, 1996;Maheswari et al, 2014). The arene oxide metabolite of CBZ may lead to hapten formation and via the immune system results in the tissue injury at the sites of hapten formation, including the liver (Leeder and Pirmohamad, 2003).…”

Section: Introductionmentioning

confidence: 99%

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Carbamazepine-induced liver injury using type 2 diabetes Spontaneously Diabetic Torii-Leprfa (SDT fatty) rats as a model for human type 2 diabetes

Takahashi

Matsuura

Toyoda

et al. 2019

Fundam. Toxicol. Sci.

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The diabetic state is considered to be one of the risk factors of drug-induced liver injury (DILI) because of the lower levels of glutathione for detoxification by conjugation with drugs. Carbamazepine (CBZ)-induced hepatotoxicity in humans is rare and unpredictable with the present state of knowledge, but it is somehow related to disturbance of glutathione metabolism, although data in this regard are limited. In order to estimate the potential risk of DILI in patients with type 2 diabetes mellitus (T2DM), we investigated the liver injury from CBZ, which is often used in the treatment of painful diabetic neuropathy in diabetic patients, using SD rats and Spontaneously Diabetic Torii-Lepr fa (SDT fatty) rats as a model for human T2DM. The SDT fatty rats appropriately mimic the diabetic state in humans and have similar profiles of glucose metabolism, hepatic function tests and glutathione synthesis to those in patients with T2DM. Short-term oral dosing with CBZ to the SDT fatty rats revealed that liver injury was detected in the SDT fatty rats but not in the SD rats and the difference was considered to be due to lower hepatic detoxification of the metabolites of CBZ by depleted hepatic glutathione synthesis. In conclusion, the potential for CBZ to induce liver injury is considered to be higher in diabetic patients than in non-diabetic humans.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Carbamazepine-induced liver injury using type 2 diabetes Spontaneously Diabetic Torii-Leprfa (SDT fatty) rats as a model for human type 2 diabetes

Takahashi

Matsuura

Toyoda

et al. 2019

Fundam. Toxicol. Sci.

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“…Isoniazid injection with NAC treated group exhibited significant increase in albumin at 7 days, significant increase in total protein and albumin after 14 and 21 days when compared with isoniazid group. These findings were in agreement with Maheswari et al, (2014). NAC has an antioxidant and hepatoprotective efficacy against the druginduced liver injury (Saleem et al, 2018) also it has the ability to avert liver malfunction and stimulate renewal of the injured cells because it has free radical scavenging and anti-oxidant abilities (Lonare et al, 2016).…”

Section: Discussionsupporting

confidence: 82%

Hepatoprotective effect of rutin and N-acetyl cysteine against isoniazid induced hepatotoxicity

Fararh

El-Shemy

Moussa

2020

Benha Veterinary Medical Journal

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This study was carried to evaluate the protective effect of rutin and N-acetyl cysteine (NAC) against isoniazid-induced hepatotoxicity (INH). In this study, seventy-two adult male rats were divided into six equal groups as follow: control group: 1 ml saline /Kg b. wt I/P. INH group: 100 mg INH /kg b. wt. I/P. INH + Rutin group: 100 mg INH /kg b. wt. I/P with 200 mg rutin /kg orally. INH + NAC group: 100 mg INH /kg b. wt. I/P with 300 mg NAC /kg orally. Rutin group: 200 mg rutin /kg/day orally. NAC group: 300 mg NAC /kg b. wt. orally. Serum and tissue specimens were collected at 7 th , 14 th and 21 st day form the 1st injection. IP injection of Isoniazid induced significant increase in values of ALT, AST, ALP, GGT and total bilirubin, while significant decrease in total protein and albumin was recorded. INH + Rutin showed significant decreases in the levels of ALT, AST, ALP and GGT with significant increase in albumin values and significant increase in total protein however significant decrease in the level of total bilirubin was recorded only at 21 days. INH + NAC induced significant decreases in the levels of ALT, AST, ALP and GGT with significant increase in albumin and total protein at 14 and 21 days and significant decrease in total bilirubin at 21 days. Rutin and NAC have potent protective effect against INH induced hepatotoxicity.

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“…In fact, the oxidation rate of every Ec (except AgEc) was significantly lower in Ringer's Lactate compared to Tris buffer, while the oxidation of LtEc was also practically negligible ( k ox = 0.04 x 10 −3 hr −1 ). This significant decrease in the oxidation rate of the Ecs in Tris buffer versus Ringer's Lactate solution may be due to the presence of two antioxidants, N ‐acetyl l ‐cysteine and sodium lactate, both of which have been shown to have antioxidant activity in vivo and in vitro, respectively …”

Section: Resultsmentioning

confidence: 99%

Direct comparison of oligochaete erythrocruorins as potential blood substitutes

Zimmerman

DiIusto

Dienes

et al. 2017

Bioengineering & Transla Med

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While many blood substitutes are based on mammalian hemoglobins (e.g., human hemoglobin, HbA), the naturally extracellular hemoglobins of invertebrates (a.k.a. erythrocruorins, Ecs) are intriguing alternative oxygen carriers. Specifically, the erythrocruorin of Lumbricus terrestris has been shown to effectively deliver oxygen in mice and rats without the negative side effects observed with HbA. In this study, the properties of six oligochaete Ecs (Lumbricus terrestris, Eisenia hortensis, Eisenia fetida, Eisenia veneta, Eudrilus eugeniae, and Amynthas gracilis) were compared in vitro to identify the most promising blood substitute candidate(s). Several metrics were used to compare the Ecs, including their oxidation rates, dissociation at physiological pH, thermal stability, and oxygen transport characteristics. Overall, the Ecs of Lumbricus terrestris (LtEc) and Eisenia fetida (EfEc) were identified as promising candidates, since they demonstrated high thermal and oligomeric stability, while also exhibiting relatively low oxidation rates. Interestingly, the O2 affinity of LtEc (P 50 = 26.25 mmHg at 37 °C) was also observed to be uniquely lower than EfEc and all of the other Ecs (P 50 = 9.29–13.62 mmHg). Subsequent alignment of the primary sequences of LtEc and EfEc revealed several significant amino acid substitutions within the D subunit interfaces that may be responsible for this significant change in O2 affinity. Nonetheless, these results show that LtEc and EfEc are promising potential blood substitutes that are resistant to oxidation and denaturation, but additional experiments will need to be conducted to determine their safety, efficacy, and the effects of their disparate oxygen affinities in vivo.

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Hepatoprotective and antioxidant activity of N-acetyl cysteine in carbamazepine-administered rats

Cited by 26 publications

References 28 publications

Carbamazepine-induced liver injury using type 2 diabetes Spontaneously Diabetic Torii-<i>Lepr<sup>fa</sup></i> (SDT fatty) rats as a model for human type 2 diabetes

Carbamazepine-induced liver injury using type 2 diabetes Spontaneously Diabetic Torii-<i>Lepr<sup>fa</sup></i> (SDT fatty) rats as a model for human type 2 diabetes

Hepatoprotective effect of rutin and N-acetyl cysteine against isoniazid induced hepatotoxicity

Direct comparison of oligochaete erythrocruorins as potential blood substitutes

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