Hepatoprotective Activity of Melittin on Isoniazid and Rifampicin Induced Liver Damage in Male Albino Rats

Naji, Khalid Mohammed; Al-Khatib, Bushra Y. H.; Al-Haj, Nora Saif; D'souza, Myrene Roslin

doi:10.1101/2020.09.08.287094

Cited by 5 publications

(7 citation statements)

References 66 publications

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“…Also, the melittin 6 mg/kg was able to show inhibitory effects on pleomorphism, mitosis, and invasion of breast cancer cells compared to the cancer control group but these effects were lower than the melittin-loaded niosome. Melittin is beneficial for the prevention of acute hepatic failure in antitubercular druginduced hepatoxicity through regulation of AST,ALT, ALP, BUN, and Total bilirubin (Naji 2020). The results of the present study were consistent with previous researchers, melittin, and melittin-loaded niosome have not toxicity effect on renal, and liver organs.…”

Section: Discussionsupporting

confidence: 92%

Delivery of melittin-loaded niosomes for breast cancer treatment: an in vitro and in vivo evaluation of anti-cancer effect

et al. 2021

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Background Melittin, a peptide component of honey bee venom, is an appealing candidate for cancer therapy. In the current study, melittin, melittin-loaded niosome, and empty niosome had been optimized and the anticancer effect assessed in vitro on 4T1 and SKBR3 breast cell lines and in vivo on BALB/C inbred mice. "Thin-layer hydration method" was used for preparing the niosomes; different niosomal formulations of melittin were prepared and characterized in terms of morphology, size, polydispersity index, encapsulation efficiency, release kinetics, and stability. A niosome was formulated and loaded with melittin as a promising drug carrier system for chemotherapy of the breast cancer cells. Hemolysis, apoptosis, cell cytotoxicity, invasion and migration of selected concentrations of melittin, and melittin-loaded niosome were evaluated on 4T1 and SKBR3 cells using hemolytic activity assay, flow cytometry, MTT assay, soft agar colony assay, and wound healing assay. Real-time PCR was used to determine the gene expression. 40 BALB/c inbred mice were used; then, the histopathology, P53 immunohistochemical assay and estimate of renal and liver enzyme activity for all groups had been done. Results This study showed melittin-loaded niosome is an excellent substitute in breast cancer treatment due to enhanced targeting, encapsulation efficiency, PDI, and release rate and shows a high anticancer effect on cell lines. The melittin-loaded niosome affects the genes expression by studied cells were higher than other samples; down-regulates the expression of Bcl2, MMP2, and MMP9 genes while they up-regulate the expression of Bax, Caspase3 and Caspase9 genes. They have also enhanced the apoptosis rate and inhibited cell migration, invasion in both cell lines compared to the melittin samples. Results of histopathology showed reduce mitosis index, invasion and pleomorphism in melittin-loaded niosome. Renal and hepatic biomarker activity did not significantly differ in melittin-loaded niosome and melittin compared to healthy control. In immunohistochemistry, P53 expression did not show a significant change in all groups. Conclusions Our study successfully declares that melittin-loaded niosome had more anti-cancer effects than free melittin. This project has demonstrated that niosomes are suitable vesicle carriers for melittin, compare to the free form.

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Section: Discussionsupporting

confidence: 92%

Delivery of melittin-loaded niosomes for breast cancer treatment: an in vitro and in vivo evaluation of anti-cancer effect

et al. 2021

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“…INH and RIF only treated group of mice (group II) had statistically significant (p < 0.01) increment of total bilirubin as compared to a normal control group of mice (group I) (Table 2). is finding was in line with the study performed by Naji et al [34] and Chandra and Shanmugapandivan [35]. is might be due to the combination of INH and RIF resulted in a higher rate of inhibition hepatic clearance of bile, an increase in lipid peroxidation in the hepatocyte, and cytochrome P450 involved in the synergistic effect of RIF and INH [34,35,44].…”

Section: Discussionsupporting

confidence: 90%

“…is finding was in line with the study performed by Naji et al [34] and Chandra and Shanmugapandivan [35]. is might be due to the combination of INH and RIF resulted in a higher rate of inhibition hepatic clearance of bile, an increase in lipid peroxidation in the hepatocyte, and cytochrome P450 involved in the synergistic effect of RIF and INH [34,35,44].…”

Section: Discussionsupporting

confidence: 90%

“…e plausible explanation of the INH and RIF that causes hepatocellular damage and attribute the elevation of the liver enzymes level in the serum is during reactive metabolites of those drugs covalently bound macromolecules of the cell (hepatocyte), resulting in depriving cellular integrity and liver enzymes released from the cell to the blood [33,34]. Additionally, these anti-TB drugs could cause cellular damage through the induction of oxidative stress as a consequence of the depletion of glutathione (GSH)/glutathione peroxidase (GPx), superoxide dismutase (SOD), and catalase (CAT) levels within hepatocytes via activation of CYP2E1 [33][34][35].…”

Section: Discussionmentioning

confidence: 99%

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Hepatoprotective Effect of Corm of Ensete ventricosum (Welw.) Cheesman Extract against Isoniazid and Rifampicin Induced Hepatotoxicity in Swiss Albino Mice

Dubiwak

Damtew

Senbetu

et al. 2021

Journal of Toxicology

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Drug-induced liver injury (DILI) is one of the cumbersome health-related problems which render approximately 50% of liver failure and patients to receiving liver transplantation every year. Antituberculosis drugs such as isoniazid and rifampicin are potentially rendering hepatotoxicity. Ensete ventricosum (Welw.) Cheesman is an herbaceous perennial plant that contributes to the indigenous ethnomedicinal values for the society. This study aimed to investigate the hepatoprotective effect of corm of Ensete ventricosum (Welw.) Cheesman extracts against isoniazid and rifampicin induced hepatotoxicity in Swiss albino mice. The study was conducted on 30 Swiss albino mice randomly allocated into five groups. Group I, group II, group III, group IV, and group V were the groups in which mice were given distilled water, only isoniazid and rifampicin, isoniazid and rifampicin along with 200 mg/kg corm of Ensete ventricosum (Welw.) Cheesman extract, isoniazid and rifampicin along with 400 mg/kg corm of Ensete ventricosum (Welw.) Cheesman extract, and isoniazid and rifampicin along with silymarin per oral per day, respectively. On the 30th day of the experiment, mice were sacrificed after anesthetized, and blood was drawn for the liver function test, and the liver was also taken from each experimental mouse for histopathological evaluation. Data were entered into EpiData version 3.1 subsequently exported to SPSS version 25 for analysis by using one-way ANOVA. Plasma alanine aminotransferase (ALT) levels, aspartate aminotransferase (AST), alkaline phosphatase (ALP), and total bilirubin (TBIL) of group II mice were significantly ( p < 0.05 ) elevated as compared to group I. The group of mice treated with a corm of Ensete ventricosum (Welw.) Cheesman at a dose of 400 mg/kg (group IV) and silymarin100 mg/kg (group V) showed a significant ( p < 0.05 ) decrease in ALT, AST, ALP, and TBIL as compared to the group II. The liver section of group II showed a change in liver architecture; however, these deformities were not noticed in group IV mice. The result showed corm of Ensete ventricosum (Welw.) Cheesman extract has a very promising hepatoprotective potential against isoniazid and rifampicin induced liver injury.

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“…Melittin is bene cial for the prevention of acute hepatic failure in antitubercular drug-induced hepatoxicity through regulate of AST,ALT, ALP,BUN and Total bilirubin [64].…”

Section: Evaluation Of Renal and Liver Enzyme Activitymentioning

confidence: 99%

Delivery of Melittin Loaded Niosomes for Breast Cancer Treatment: an in-vitro and in-vivo Evaluation of Anti-cancer Effect

Moghaddam

Akbarzadeh

Marzbankia

et al. 2020

Preprint

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BackgroundMelittin, a peptide component of honey bee venom, is an appealing candidate for cancer therapy. In the current study, Melittin and Melittin loaded niosome had been optimized and assessed the anticancer effect an In-Vitro on 4T1 and SKBR3 breast cell lines and In-Vivo on BALB/C inbred mice. "Thin-layer hydration method" was used for preparing the Niosomes; different niosomal formulations of Melittin were prepared and characterized in terms of morphology, size, Polydispersity index, encapsulation efficiency, release kinetics, and stability. A niosome was formulated and loaded with Melittin as a promising drug carrier system for chemotherapy of the breast cancer cells. Hemolysis, apoptosis, cell cytotoxicity, invasion and migration of selected concentrations of Melittin, and Melittin loaded niosome were evaluated on 4T1 and SKBR3 cells using hemolytic activity assay, flow cytometry, MTT assay, soft agar colony assay, and wound healing assay. Real-time PCR was used to determine the genes expression. 35 BALB/c inbred mice were used; then, the histopathology, P53 immunohistochemical assay and estimate of renal and liver enzyme activity for all groups had been done.Results: This study showed Melittin loaded niosome is an excellent substitute in breast cancer treatment due to enhanced targeting, encapsulation efficiency, PDI, and release rate and shows a high anticancer effect on cell lines. The Melittin loaded niosome affect the genes expression by studied cells were higher than other samples; down-regulates the expression of Bcl2, MMP2, and MMP9 genes while they up-regulate the expression of Bax, Caspase3 and Caspase9 genes. Also enhanced the apoptosis rate and inhibitored cell migration, invasion in both cell lines compared to the Melittin samples. Results of histopathology showed reduce mitosis index, invasion and pleomorphism in Melittin loaded niosome. Renal and hepatic biomarker activity did not show a significant difference in Melittin loaded niosome and Melittin compared to healthy control. In immunohistochemistry, P53 expression did not show a significant change in all groups.Conclusions: Our study successfully declares that Melittin loaded niosome had more anti-cancer effects than free Melittin. This project has demonstrated that Niosomes are suitable vesicle carriers for Melittin, compare to free form.

show abstract

Hepatoprotective Activity of Melittin on Isoniazid and Rifampicin Induced Liver Damage in Male Albino Rats

Cited by 5 publications

References 66 publications

Delivery of melittin-loaded niosomes for breast cancer treatment: an in vitro and in vivo evaluation of anti-cancer effect

Delivery of melittin-loaded niosomes for breast cancer treatment: an in vitro and in vivo evaluation of anti-cancer effect

Hepatoprotective Effect of Corm of Ensete ventricosum (Welw.) Cheesman Extract against Isoniazid and Rifampicin Induced Hepatotoxicity in Swiss Albino Mice

Delivery of Melittin Loaded Niosomes for Breast Cancer Treatment: an in-vitro and in-vivo Evaluation of Anti-cancer Effect

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