Ammara Saleem

Textile industrial effluent induces mutagenicity and oxidative DNA damage and exploits oxidative stress biomarkers in rats.

Exposure to complex mixtures like textile effluent poses risks to animal and human health such as mutations, genotoxicity and oxidative damage. Aim of the present study was to quantify metals in industrial effluent and to determine its mutagenic, genotoxic and cytotoxic potential and effects on oxidative stress biomarkers in effluent exposed rats. Metal analysis revealed presence of high amounts of zinc, copper, chromium, iron, arsenic and mercury in industrial effluent. Ames test with/without enzyme activation and MTT assay showed strong association of industrial effluent with mutagenicity and cytotoxicity respectively. In-vitro comet assay revealed evidence of high oxidative DNA damage. When Wistar rats were exposed to industrial effluent in different dilutions for 60 days, then activities of total superoxide dismutase and catalase and hydrogen peroxide concentration were found to be significantly lower in kidney, liver and blood/plasma of effluent exposed rats than control. Vitamin C in a dose of 50 mg/kg/day significantly reduced oxidative effects of effluent in rats. On the basis of this study it is concluded that industrial effluent may cause mutagenicity, in-vitro oxidative stress-related DNA damage and cytotoxicity and may be associated with oxidative stress in rats. Vitamin C may have ameliorating effect when exposed to effluent.

Genotoxic and cytotoxic potential of Alternanthera Bettzickiana, an important ethno-medicinal plant

The present study was carried out to investigate the mutagenic and cytotoxic potential of n-hexane and aqueous-methanolic whole plant extracts of Alternanthera bettzickiana. Aqueous-methanolic and n-hexane extracts of Alternanthera bettzickiana extracts were assessed for the mutagenic potential with Salmonella tester strains TA-100 and TA-102 in the presence and absence of the rodent enzyme activation system and cytotoxic potential was assessed by MTT assay. Aqueous-methanolic extract showed the presence of saponins, tannins, terpenoids, flavonoids and glycosides. However n-hexane extract revealed the presence of tannins and terpenoids only. It was found that a concentration as low as 15mg/mL of both extracts was more mutagenic to the TA 102 tester strain than TA-100. Hexane whole plant extract of Altenanthera bettzickiana was more mutagenic than aqueous-methanolic extract considering revertant colonies of TA 100 strain. Aqueous-methanolic and n-hexane whole plant extracts of Altenanthera bettzickiana showed higher mutagenic potential in the presence of the enzyme activation system. Mutagenicity of aqueous-methanolic extract increased with an enzyme activation system in case of TA 100 whereas mutagenicity of n-hexane extract decreased in the presence of the enzyme activation system with TA 100 and TA 102 strains. Aqueous-methanolic and n-Hexane whole plant extracts of Alternanthera bettzickiana showed an IC-50 of 493 and 456 µg/mL in BHK-21 cells respectively. It can be concluded that Altenanthera bettzickiana exhibited mutagenic activity in a bacterial reverse mutation assay with and without enzyme activation systems. However, it showed limited cytotoxicity to BHK-21 cells.

Current trends in the treatment of hepatitis C: interventions to avoid adverse effects and increase effectiveness of anti-HCV drugs.

Viral hepatitis, an inflammatory liver disease, is caused by various genotypes of hepatitis C viruses (HCV). Hepatitis C slowly sprouts into fibrosis, which progresses to cirrhosis. Over a prolonged period of time compensated cirrhosis can advance to decompensated cirrhosis culminating in hepatic failure and death. Conventional treatment of HCV involves the administration of interferons. However, association of interferon with the adverse drug reactions led to the development of novel anti-HCV drugs given as monotherapy or in combination with the other drugs. Advances in drug delivery systems (DDS) improved the pharmacokinetic profile and stability of drugs, ameliorated tissue damages on extravasation and increased the targeting of affected sites. Liposomes and lipid based vehicles have been employed with polyethylene glycol (PEG) so as to stabilize the formulations as PEG drug complex. Sofosbuvir, a novel anti-HCV drug, is administered as monotherapy or in combination with daclatasvir, ledipasivir, protease inhibitors, ribavirin and interferon for the treatment of HCV genotypes 1, 2 and 3. These drug combinations are highly effective in eradicating the interferon resistance, recurrent HCV infection in liver transplant, concurrent HIV infection and preventing interferon related adverse effects. Further investigations to improve drug targeting and identification of new drug targets are highly warranted due to the rapid emergence of drug resistance in HCV.

A Comprehensive Review on Ethnomedicinal, Pharmacological and Phytochemical Basis of Anticancer Medicinal Plants of Pakistan

The widespread emergence of cancer and development of resistance to chemotherapeutic agents is increasing the interest of scientists in the use of ethnomedicinal preparations and isolated phytochemicals in the treatment and prevention of disease. Medicinal plants have been used in Pakistan since prehistoric times. The present review was designed to identify anticancer plants of ethnomedicinal significance and to summarize the anticancer activities carried out on these medicinal plants to establish the pharmacological and phytochemical basis of their use. Pakistani anticancer medicinal plants of ethnopharmacological significance were reviewed. Conservation status, worldwide distribution and ethno-botanical preparations of these medicinal plants were also tabulated. These medicinal plants and their isolated phytochemicals were also explored for their anticancer activities. It was revealed that there were 108 anticancer medicinal plants used to treat different neoplastic conditions on the folklore basis throughout Pakistan. Among these anticancer plants, 64 plants were found to be investigated previously for anticancer activity through in vivo and in vitro methods. Several ethnomedicinal plants have been validated for their anticancer activities through in vitro and animal models. These medicinal plants and phytochemicals resulted in the inhibition of initiation, progression or metastasis of neoplasm. Some medicinal plants (10) are endangered species. Half of folkloric Pakistani plants have been validated for use against various cancers through in vitro or in vivo methods. It is necessary to carry out further pharmacological and toxicological evaluation of these folkloric anticancer plants of Pakistan. It is also necessary to identify and isolate further potential phytochemicals so as to be evaluated in cancer patients.

Increasing beta cell mass to treat diabetes mellitus.

Finding a radical cure for diabetes has reached paramount importance in medicine due to the widespread prevalence of the disease. A substantial reduction in insulin-secreting beta cells is evident in diabetes. The failure of cyclin-dependent kinases (CDKs) and cyclins to access the nucleus is responsible for quiescence or senescence in human and rodent beta cells. The augmentation of beta cell proliferation is supposed to reverse diabetes. This concept has inspired the discovery of newer drugs that encourage the proliferation of beta cells. Although it is a rational step towards a cure for diabetes, the differences in biochemical pathways in rodents and human beta cells pose difficulty in promoting the proliferation of human beta cells. Primarily, it is mandatory to clearly understand the intracellular pathways involved in the proliferation of beta cells so as to pave the way for therapeutic interventions. There are several intrinsic factors that trigger the proliferation of beta cells. Furthermore, it is also obvious that the early death of beta cells due to oxidative stress-related upregulation of pro-apoptotic genes also predisposes individuals to diabetes mellitus. Polyphenols, exendin 4, histone deacetylase inhibitors, glucagon-like peptide 1, phenyl pyruvic acid glucoside, and several flavonoids reduce the early apoptosis of beta cells partly through their role in the reduction of oxidative stress. A better understanding of intracellular pathways, the identification of specific mitogens, the induction of beta cell proliferation, and the inhibition of apoptosis may help us treat diabetes mellitus through an increase in beta cell mass.

Chemical characterisation and hepatoprotective potential of Cosmos sulphureus Cav. and Cosmos bipinnatus Cav.

Abstract This study was conducted to validate the hepatoprotective activity of Cosmos sulphureus and Cosmos bipinnatus. Aqua-methanolic extracts of both plants were evaluated for the presence of various phyto-constituents through HPLC. Different doses of both plant extracts were administered to rats for nine days. Standard control was silymarin 100 mg/kg. Paracetamol 1 gm/kg was administered 3 h post treatment on 9th day for induction of hepatotoxicity. Blood was collected for the evaluation of liver biochemical markers and livers were removed for histopathological evaluation 24 h post-paracetamol treatment. HPLC analysis revealed the presence of quercetin, gallic acid, caffeic acid and chlorogenic acid in both plant extracts. The extracts of both plants decreased the level of alanine aminotransaminase and total bilirubin significantly (p < 0.05), dose dependently and protected hepatocytes from paracetamol-induced hepatotoxicity. It can be concluded that both plants may possess hepatoprotective activity possibly due to the presence of quercetin and phenolic compounds.

ANTI-INFLAMMATORY, ANTI-NOCICEPTIVE AND ANTIPYRETIC POTENTIAL OF TERMINALIA CITRINA FRUIT EXTRACTS

Background: Plants and herbs have long been used as remedies without scientific evidences. The objective of the present study was to explore the anti-inflammatory, anti-nociceptive and antipyretic potential of ethanolic and aqueous extracts of Terminalia citrina fruits in mice. Materials and Methods: Extracts of Terminalia citrina fruits were evaluated at doses of 200mg/kg, 400mg/kg and 600mg/kg in albino mice for preventive effect in inflammatory edema, peripheral pain sensation and pyrexia. Carrageenan induced paw edema method was utilized to evaluate anti-inflammatory activity. Analgesic appraisal of extracts was demonstrated using acetic acid induced writhing model of pain. Antipyretic potential was determined by brewer’s yeast induced pyrexia model. Statistical analysis was conducted by ANOVA following post hoc test. Results: Both extracts exhibited significant and dose-dependent anti-inflammatory, analgesic and antipyretic activities. The ethanolic extract was more effective in reducing inflammatory edema, pyrexia and pain sensation than aqueous extracts in all tested doses. Conclusion: It can be concluded that fruit extracts of Terminalia citrina may be effective in reducing inflammation, pyrexia and pain sensation in animals.