Concurrent Inflammation Augments Antimalarial Drugs-Induced Liver Injury in Rats

Niknahad, Hossein; Heidari, Reza; Firuzi, Roya; Abazari, Farzaneh; Ramezani, Maral; Azarpira, Negar; Hosseinzadeh, Massood; Najibi, Asma; Saeedi, Arastoo

doi:10.15171/apb.2016.076

Cited by 14 publications

(13 citation statements)

References 52 publications

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“…17,64 Hepatic inflammation plays an essential role in the pathogenesis of liver injury in the thioacetamide model, 66 or other types of xenobiotics-induced hepatotoxicity. 27,67 In the current study we found that inflammatory cells infiltration was significantly lower in boldine-treated groups (Figure 2). Hence, the effect of boldine treatment on hepatic inflammation and inflammatory mediators could be the subject of further research in this field.…”

Section: Discussionsupporting

confidence: 57%

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Boldine Supplementation Regulates Mitochondrial Function and Oxidative Stress in a Rat Model of Hepatotoxicity

et al. 2019

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Background: The xenobiotics-induced liver injury is a clinical complication. Hence, finding new hepatoprotective strategies has clinical value. Oxidative stress and its subsequent complications are major mechanisms involved in xenobiotics-induced hepatotoxicity. Boldine is one of the most potent antioxidant molecules widely investigated for its protective properties in different experimental models. In the current study, the hepatoprotective properties of boldine and its potential mechanisms of hepatoprotection have been investigated. Methods: Rats received thioacetamide (TAA; 200 mg/kg, i.p) as a model of acute liver injury. Boldine (5, 10, 1nd 20 mg/kg; 24 hours intervals; oral) was administered as the hepatoprotective agent. Results: Liver injury was evident in TAA-treated animals (48 hours after TAA exposure) as a severe increase in serum level of liver injury biomarkers and histopathological alterations. Moreover, markers of oxidative stress were increased in liver tissue of TAA-treated rats. Assessment of mitochondrial indices of functionality revealed a significant decrease in mitochondrial dehydrogenases activity, the collapse of mitochondrial membrane potential, mitochondrial swelling and depletion of ATP content. It was found that boldine supplementation mitigated liver tissue markers of oxidative stress and improved mitochondrial indices of functionality in TAA-treated animals. Conclusion: The hepatoprotective properties of boldine might primarily rely on antioxidant and mitochondria protecting effects of this alkaloid.

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Section: Discussionsupporting

confidence: 57%

“…Samples were mixed and heated (100 °C, for 45 minutes). 27 After the incubation period, the mixture was cooled, and then 2 mL of n-butanol was added. Samples were vigorously vortexed and centrifuged (10000 g for 5 minutes).…”

Section: Lipid Peroxidation In Liver Tissuementioning

confidence: 99%

Boldine Supplementation Regulates Mitochondrial Function and Oxidative Stress in a Rat Model of Hepatotoxicity

et al. 2019

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“…10,30 The mechanisms of hepatic injury related to HCQ are poorly established, and toxicity may be due to reactive metabolites and oxidative stress induced by this drug or an idiosyncratic toxic or synergistic effect associated with inflammatory processes. 26,31,32 Referring to an experimental rat model, Nikanahad et al have suggested that concomitant inflammatory processes, including those induced by infections such as malaria, may increase liver damage caused by antimalarial drugs. 32 Therefore, the potential deleterious synergistic effect of COVID-19 infection and antimalarial drugs needs to be assessed.…”

Section: Discussionmentioning

confidence: 99%

“…26,31,32 Referring to an experimental rat model, Nikanahad et al have suggested that concomitant inflammatory processes, including those induced by infections such as malaria, may increase liver damage caused by antimalarial drugs. 32 Therefore, the potential deleterious synergistic effect of COVID-19 infection and antimalarial drugs needs to be assessed. 33 Although beyond the scope of this discussion, the case also highlights the high degree of transmissibility of SARS-CoV-2, which reached all family members in a short period, all of whom tested positive according to RT-PCR.…”

Section: Discussionmentioning

confidence: 99%

Case Report: Hepatotoxicity Associated with the Use of Hydroxychloroquine in a Patient with COVID-19

Falcão

Cavalcanti

Filho

et al. 2020

The American Journal of Tropical Medicine and Hygiene

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Hydroxychloroquine (HCQ) has been used for the treatment of novel coronavirus disease cases. However, evidence of efficacy remains limited, and adverse events can be associated with its use. Here, we report a case of a patient with severe COVID-19 who, after being administered HCQ, exhibited a 10-fold increase in serum levels of transaminases, followed by a rapid decrease after HCQ was withdrawn. Considering the significantly increased use of HCQ during the COVID-19 pandemic, this case alerts us to the potential for HCQ to be associated with hepatotoxicity and the need to monitor liver function during HCQ therapy.

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“…However, the postulated immune protection provided by prior malaria infection does not protect against the negative effects of inflammation. Additionally, various antimalarial drugs employ oxidative stress as a mechanism for parasite clearance [ 60 ]. More so, mild inflammation coupled with drug-induced oxidative stress can cause unintended organ damage [61].…”

Section: Effects Of Covid-19 and Malaria On Pathogenesis Of Diabetmentioning

confidence: 99%

Implications of COVID-19 Pandemic on Evolution of Diabetes in Malaria-Endemic African Region

Acquah

2020

Journal of Diabetes Research

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The coronavirus disease 2019 (COVID-19) pandemic continues to cause havoc to many countries of the globe, with no end in sight, due to nonavailability of a given vaccine or treatment regimen. The pandemic has so far had a relatively limited impact on the African continent, which contributes more than 93% of global malaria burden. However, the limited burden of COVID-19 pandemic on the African region could have long-term implications on the health and wellbeing of affected inhabitants due to its malaria-endemic status. Malaria causes recurrent insulin resistance with episodes of infection at relatively low parasitaemia. Angiotensin-converting enzyme 2 (ACE2) which is widely distributed in the human body is implicated in the pathogenesis of malaria, type 2 diabetes mellitus (T2DM), and COVID-19. Use of ACE2 by the COVID-19 virus induces inflammation and oxidative stress, which can lead to insulin resistance. Although COVID-19 patients in malaria-endemic African region may not exhibit severe signs and symptoms of the disease, their risk of exhibiting heightened insulin resistance and possible future development of T2DM is high due to their prior exposure to malaria. African governments must double efforts at containing the continued spread of the virus without neglecting existing malarial control measures if the region is to avert the plausible long-term impact of the pandemic in terms of future development of T2DM.

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Concurrent Inflammation Augments Antimalarial Drugs-Induced Liver Injury in Rats

Cited by 14 publications

References 52 publications

Boldine Supplementation Regulates Mitochondrial Function and Oxidative Stress in a Rat Model of Hepatotoxicity

Boldine Supplementation Regulates Mitochondrial Function and Oxidative Stress in a Rat Model of Hepatotoxicity

Case Report: Hepatotoxicity Associated with the Use of Hydroxychloroquine in a Patient with COVID-19

Implications of COVID-19 Pandemic on Evolution of Diabetes in Malaria-Endemic African Region

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