Pharmacological Evaluation of Gatifloxacin in Chemically Induced Hepatocarcinogenesis: A New Tool for Hepatocellularcarcinoma Treatment

Afzal, Muhammad; Kazmi, Imran; Khan, Ruqaiyah; Singh, Rajbala; Pravez, Mohammad; Imam, Faisal; Anwar, Firoz

doi:10.4172/1948-5956.1000179

Cited by 5 publications

(3 citation statements)

References 17 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…30 Problem with the regulation of apoptosis have been correlated with a number of diseases and is also well established reason for the occurrence of cancer. 32 AFP has to be considered as 'the gold standard' for HCC serum markers. Thus, cancer cells are more proliferative than normal.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Fixed dose combination therapy loperamide and niacin ameliorates diethylnitrosamine-induced liver carcinogenesis in albino Wistar rats

et al. 2015

Self Cite

View full text Add to dashboard Cite

BackgroundHepatocellular Carcinoma (HCC) is among the most lethal cancers (five-year survival rates under 11%), which makes it the third most frequent cause of cancer related deaths in men and sixth in women. Still there are limited treatments available for majority of HCC at advanced stages. Systemic chemotherapy for advanced hepatocellular carcinomas, either as single-agent therapy or in combination, radiofrequency ablation or recently introduced tyrosine kinase inhibitors, e.g. sorafenib are some to bank upon.Aim: This study is an attempt to evaluate the synergistic chemopreventive potential of Loperamide (5mg/kg) in combination with Niacin in hepatocarcinogenic rats. When challenged by a single diethylnitrosamine (DENA) (160 mg/kg). Material and methods:The ability to treat hepatocellular carcinoma was measured by comparing biochemical serum markers such as glutamate oxaloacetate transaminase (SGOT), serum glutamate pyruvate transaminase (SGPT), alkaline phosphatase (ALP), acid phophatase (AP), cholesterol (C), triglycerides (TG) and high density lipoproteins (HDL), total proteins (TPR), bilirubin and the specific marker for hepatocellular carcinoma such as alpha fetoprotein (AFP). The caspase-3 activity was also evaluated to decipher the potential of the drug as well as to explore the possible mechanism. Results:The results have revealed the significant elevation of these parameters in DENA control group compared to normal control and the therapeutic groups. Casepase-3 activity was found to be highly elevated in the therapeutic group. Histopathology result also revealed severe the changes in hepatic tissues. Disease control animals showed central veins surrounded by extensive necrosis and inflammatory infiltrate, clusters of hepatocyte necrosis and the portal tract with bile duct proliferation and marked atypia. Liver section from loperamide with niacin control group shows the normal architecture of the liver, no necrosis was observed. ConclusionOur data indicates that this remarkable combination possess the potential for the treatment of hepatocellular carcinomas in rats exposed to DENA. Administration of Loperamide + Niacin relatively improved the biochemical parameters to values approximating those of the normal controls via increasing the Caspase-3 activity in them and inducing Apoptosis in cancerous cells.

show abstract

Section: Discussionmentioning

confidence: 99%

“…Moreover, AFP is a serum protein, showing higher specicity for HCC. 32 AFP has to be considered as 'the gold standard' for HCC serum markers.…”

Section: Discussionmentioning

confidence: 99%

Fixed dose combination therapy loperamide and niacin ameliorates diethylnitrosamine-induced liver carcinogenesis in albino Wistar rats

et al. 2015

Self Cite

View full text Add to dashboard Cite

show abstract

“…Preparation of DEN carcinogen was completed using the method given by Kazmi et al, 2014 as modified by Afzal et al, 25 DEN (200 mg kg −1 ) was dissolved in the phosphate buffer saline (PBS) ( pH = 4.5).…”

Section: Preparation Of Denmentioning

confidence: 99%

Umbelliferone β-d-galactopyranoside inhibits chemically induced renal carcinogenesis via alteration of oxidative stress, hyperproliferation and inflammation: possible role of NF-κB

et al. 2015

View full text Add to dashboard Cite

Umbelliferone (7hydroxycoumarin) compound possesses strong anti-inflammatory and free radical scavenging activity. The intend of the current study was to conclude the renalprotective efficacy of Umbelliferone β-D-galactopyranoside (UFG) over diethylinitrosamine (DEN) initiated and ferric nitrilotriacetate (Fe-NTA) promoted the oxidative stress, inflammation and renal injury in Wistar rats. The capacity of UFG to scavenge the reactive nitrogen species (RNS) and reactive oxygen species (ROS) was evaluated and its also scrutinized scavenging against the hydroxyl (OH), superoxide (O 2 ), nitric acid (NO) and hydrogen peroxide (H 2 O 2 ) radicals. Renal carcinoma was induced by single intraperitoneal injection of DEN (200 mg/kg, b.w.) and promoted by twice weekly treatment of Fe-NTA (9 mg/kg, b.w.) for 22 weeks. To estimated the molecular mechanism implicated in the antitumor potential of UFG, its consequence was appraised on renal tumor inflammation; proinflammatory cytokines including interleukin-1β (IL-1β), interlukin-6 (IL-6) and tumor necrosis factor (TNF-α); inflammatory mediator including prostaglandin E 2 (PGE 2 ), ornithine decarboxylase (ODC) and nuclear factor kappa B cell (NFκB). It's also induced the serum abnormability including creatinine, lactate dehydrogensae (LDH) blood urea nitrogen (BUN) and [ 3 H] thymidine incorporation. Further, augments the renal lipid peroxidation (LPO), endogenous antioxidant enzymes, phase II metabolizing enzymes and concomitant reduction in glutathione (GSH). UFG showed the 95% and 99% antioxidant activity in 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) and 2, 2-diphenyl-1-picrylhydrazyl (DPPH) model. UFG significantly inhibited the RNS and ROS radical and 2 indicated the antioxidant activity (in vitro). The results showed momentous renal markers and oxidative stress protection impaired by UFG. UFG also restored the altered inflammatory and proinflammatory cytokines, which further strengthens the renal protection of UFG in DEN+Fe-NTA induced renal carcinogenesis. These results recommend that UFG as an efficient chemoprotective agent having the ability to thwart the DEN induced and Fe-NTA promoted renal carcinoma in experimental rats.

show abstract

Chemomodulatory effect Melastoma Malabathricum Linn against chemically induced renal carcinogenesis rats via attenuation of inflammation, oxidative stress, and early markers of tumor expansion

et al. 2016

View full text Add to dashboard Cite

Melastoma malabathricum Linn (MM) has high valued for its commercial significance. Indian market (northeast) has great demand for the plants, which extended, its use as a traditional home remedy due to its anti-inflammatory effects. In this study, we scrutinize the therapeutic and protective effect of MM against diethylnitrosamine (DEN) and ferric nitrilotriacetate (Fe-NTA)-induced renal carcinogenesis, renal hyperproliferation, and oxidative stress in rats. Liquid chromatography mass spectroscopy (LC-MS) was used for identification of phytoconstituents. Administration of DEN confirmed the initiation the renal carcinogenesis via enhancing the expansion of tumor incidence. Intraperitoneally, administration of Fe-NTA boost the antioxidant enzymes (phase I), viz., superoxide dismutase (SOD), catalase (CAT), glutathione reductase (GR), glutathione peroxidase (GPx) and phase II, viz., quinone reductase (QR) and glutathione-S-transferase (GST). It also increased the content of renal lipid peroxidation (LPO), hydrogen peroxidase (HO) with decrease content in glutathione content (GSH). It also increased the renal biochemical and non-biochemical parameter. It also confirmed the augment the level of thymidine [3H] incorporation into renal DNA, ornithine decarboxylase (ODC) activity and increased the generation of proinflammatory (TNF-α, IL-6 and IL-β) and inflammatory mediator (PGE). We also analyzed the macroscopic and histologic of renal tissue. In addition, the effect of phytoconstituent of MM extract was evaluated in silico and free radical scavenging activity against the DPPH and ABTS free radicals. LC-MS confirmed the presence of quercetin >gallic acid in MM extract. Renal carcinogenesis rats treated with MM (100, 250, and 500 mg/kg) confirmed the significantly (P < 0.001) protective effect via reduction the antioxidant (phase I and phase II) enzymes, biochemical parameter and restore the proinflammatory and inflammatory mediator at dose dependent manner. MM altered the ODC and thymidine activity in renal DNA. The chemoprotective effect of MM was confirmed via decreased the renal tumor incidence, which was confirmed by the macroscopic and histopathological observation. Consequently, our result suggests that MM is a potent chemoprotective agent and suppresses DEN+ Fe-NTA-induced renal carcinogenesis, inflammatory reaction, and oxidative stress injury in Wister rats.

show abstract

Pharmacological Evaluation of Gatifloxacin in Chemically Induced Hepatocarcinogenesis: A New Tool for Hepatocellularcarcinoma Treatment

Cited by 5 publications

References 17 publications

Fixed dose combination therapy loperamide and niacin ameliorates diethylnitrosamine-induced liver carcinogenesis in albino Wistar rats

Fixed dose combination therapy loperamide and niacin ameliorates diethylnitrosamine-induced liver carcinogenesis in albino Wistar rats

Umbelliferone β-d-galactopyranoside inhibits chemically induced renal carcinogenesis via alteration of oxidative stress, hyperproliferation and inflammation: possible role of NF-κB

Chemomodulatory effect Melastoma Malabathricum Linn against chemically induced renal carcinogenesis rats via attenuation of inflammation, oxidative stress, and early markers of tumor expansion

Contact Info

Product

Resources

About