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Fulltext Role of the CYP1A2 Gene Polymorphism on Early Ageing from Occupational Exposure

Eshkoor S, Ismail P, Rahman S, Moin S, Adon M

Balkan J Med Genet, 2013 Dec;16(2):45-52.
PMID: 24778563 DOI: 10.2478/bjmg-2013-0031

The ageing process is influenced by many internal and external factors. The toxic substances in the environment can cause genomic damages to cells, which increase the risk of early ageing. Furthermore, the cytochrome P450 1A2 (CYP1A2) gene polymorphism is a susceptibility factor and may enhance the risk of DNA damage in cells. The current study was carried out to show whether occupational exposure could cause genotoxicity in cells carrying the CYP1A2 gene polymorphism, thus enhancing the likelihood of early ageing. This study was conducted on mechanical workshop workers and a control group by collecting buccal cells from their mouths. Restriction fragment length polymorphism-polymerase chain reaction (RFLP-PCR) was used to identify the CYP1A2 gene polymorphism in the cells. In addition, three extra methods including micronuclei (MN) test, comet assay and real-time PCR (RT-PCR) were applied to determine the effects of gene polymorphisms on DNA damage and ageing from occupational exposure. The results showed that DNA damage in the cells carrying the mutated genotype was higher than the wild genotype. In addition, the difference in MN frequency (p = 0.001) and relative telomere length (p = 0.002) between workers and controls was significant (p <0.05) in the mutated genotype. The findings indicated a possible protective effect of gene polymorphism against early ageing, which was characterized by lack of a significant influence of CYP1A2 gene polymorphism on genetic material in the subjects (p >0.05). It was concluded that the CYP1A2 gene could be a contributing factor to prevent early ageing from occupational exposure.
Does GSTP1 polymorphism contribute to genetic damage caused by ageing and occupational exposure?

Eshkoor SA, Ismail P, Rahman SA, Moin S

Arh Hig Rada Toksikol, 2011 Dec;62(4):291-8.
PMID: 22202462 DOI: 10.2478/10004-1254-62-2011-2088

The aim of our study was to see the effects of GSTP1 polymorphism on biomarkers of ageing, including micronuclei (MN), comet tail length, and relative telomere length in automobile repair workers, who are exposed to a broad spectrum of potential mutagens. The analysis was performed on buccal cells collected from occupationally exposed and non-exposed (control) subjects. Samples were analysed using cytogenetic and molecular methods, including restriction fragment length polymorphism (RFLP), MN test, comet assay, and real-time PCR. The results confirmed the DNA damaging effects of substances used in the mechanical workshops, but did not confirm the influence of GSTP1 gene polymorphism on DNA damage. However, further studies on both occupationally exposed and control populations are needed to understand the relationship between GSTP1 polymorphism and genome damage.
Antinociceptive effect of Melastoma malabathricum ethanolic extract in mice

Sulaiman MR, Somchit MN, Israf DA, Ahmad Z, Moin S

Fitoterapia, 2004 Dec;75(7-8):667-72.
PMID: 15567242

The antinociceptive effect of the ethanolic extract of Melastoma malabathricum (MME) was investigated using acetic acid-induced abdominal writhing test and hot-plate test in mice. It was demonstrated that the extract (30-300 mg/kg, i.p.) strongly and dose-dependently inhibited the acetic acid-induced writhing with an ED(50) of 100 (78-160) mg/kg i.p. It also significantly increased the response latency period to thermal stimuli. Furthermore, the nonselective opioid receptor antagonist, naloxone blocked the antinociceptive effect of the extract in both tests, suggesting that M. malabathricum may act both at peripheral and central levels.
Antinociceptive and antiedematogenic activities of andrographolide isolated from Andrographis paniculata in animal models

Sulaiman MR, Zakaria ZA, Abdul Rahman A, Mohamad AS, Desa MN, Stanslas J, et al.

Biol Res Nurs, 2010 Jan;11(3):293-301.
PMID: 19689990 DOI: 10.1177/1099800409343311

The current study was performed to evaluate the antinociceptive and antiedematogenic properties of andrographolide isolated from the leaves of Andrographis paniculata using two animal models. Antinociceptive activity was evaluated using the acetic acid- induced writhing and the hot-plate tests, while antiedematogenic activity was measured using the carrageenan-induced paw edema test. Subcutaneous (s.c.) administration of andrographolide (10, 25, and 50 mg/kg) did not affect the motor coordination of the experimental animals but produced significant (p < .05) antinociceptive activity when assessed using both tests. However, 2 mg/kg naloxone failed to affect the 25 mg/kg andrographolide activity in both tests, indicating that the activity was modulated via nonopioid mechanisms. Furthermore, andrographolide showed significant (p < .05) antiedematogenic activity. In conclusion, the results obtained suggest that andrographolide has antinociceptive and antiedematogenic activities; it may be useful for treating pain and inflammation once human studies are conducted.
Evaluation of the antinociceptive activity of Ficus deltoidea aqueous extract

Sulaiman MR, Hussain MK, Zakaria ZA, Somchit MN, Moin S, Mohamad AS, et al.

Fitoterapia, 2008 Dec;79(7-8):557-61.
PMID: 18672036 DOI: 10.1016/j.fitote.2008.06.005

The aqueous extract of Ficus deltoidea leaves was evaluated for possible antinociceptive activity in three models of nociception, namely, acetic acid-induced abdominal writhing, formalin and hot plate test. The results of the present study showed that intraperitoneal administration of the F. deltoidea leaves aqueous extract at the dose of 1, 50 and 100 mg/kg, 30 min prior to pain induction produced significant dose-dependent antinociceptive effect in all the models used, which indicating the presence of both central and peripherally mediated activities. Furthermore, the antinociceptive effect of the extract in the formalin and hot plate test was reversed by the non-selective opioid receptor antagonist naloxone suggesting that the endogenous opioid system is involved in its analgesic mechanism of action. Thus, the present results demonstrated that F. deltoidea leaves aqueous extract contains pharmacologically active constituents which possess antinociceptive activity justifying its popular therapeutic use in treating conditions associated with the painful conditions.
Antinociceptive and antiinflammatory activities of the aqueous extract of Trigonopleura malayana resin in experimental animal models

Sulaiman MR, Zakaria ZA, Kamaruddin A, Meng TF, Ali DI, Moin S

Methods Find Exp Clin Pharmacol, 2008 Nov;30(9):691-6.
PMID: 19229377 DOI: 10.1358/mf.2008.30.9.1305824

Trigonopleura malayana L. (Euphorbiaceae) resin, locally known as Gambir Sarawak, has been used traditionally to alleviate pain associated with insect bites, muscle ache, toothache and minor injuries. The present study was carried out using various animal models to determine the antinociceptive and antiinflammatory activities of the T. malayana resin aqueous extract. Antinociceptive activity was measured using the abdominal constriction, hot plate and formalin tests, while antiinflammatory activity was measured using the carrageenan-induced paw edema test. The extract, obtained after 24 h of soaking the dried resin in distilled water, was prepared in doses of 0.3, 3 and 10 mg/kg and administered subcutaneously 30 min prior to the assays. The mechanism of action was also determined by prechallenging with naloxone (10 mg/kg), a nonselective opioid antagonist. The extract was found to exhibit significant (P < 0.05) and dose-dependent antinociceptive and antiinflammatory activities; naloxone failed to inhibit the former activity. In conclusion, the aqueous extract of T. malayana resin possesses nonopioid antinociceptive and antiinflammatory activities, thus supporting previous claims regarding its traditional use by the Malays to treat various ailments, particularly those related to pain.
Association of insertion/deletion polymorphism of angiotensin-converting enzyme gene with essential hypertension and type 2 diabetes mellitus in Malaysian subjects

Ramachandran V, Ismail P, Stanslas J, Shamsudin N, Moin S, Mohd Jas R

J Renin Angiotensin Aldosterone Syst, 2008 Dec;9(4):208-14.
PMID: 19126661 DOI: 10.1177/1470320308097499

The deletion (D) allele of the angiotensin-converting enzyme (ACE) gene has been studied in various populations in relation to hypertension (HTN) and type 2 diabetes mellitus (T2DM) with contradictory results. This study sought to determine the association of insertion (I)/D polymorphism of the ACE gene in hypertensive and T2DM subjects in a Malaysian population.
Antinociceptive activity of the essential oil of Zingiber zerumbet

Sulaiman MR, Tengku Mohamad TA, Shaik Mossadeq WM, Moin S, Yusof M, Mokhtar AF, et al.

Planta Med, 2010 Feb;76(2):107-12.
PMID: 19637111 DOI: 10.1055/s-0029-1185950

In the present study, the rhizome essential oil from Zingiber zerumbet (Zingiberaceae) was evaluated for antinociceptive activity using chemical and thermal models of nociception, namely, the acetic acid-induced abdominal writhing test, the hot-plate test and the formalin-induced paw licking test. It was demonstrated that intraperitoneal administration of the essential oil of Z. zerumbet (EOZZ) at the doses of 30, 100 and 300 mg/kg produced significant dose-dependent inhibition of acetic acid-induced abdominal writhing, comparable to that of obtained with acetylsalicylic acid (100 mg/kg). At the same doses, the EOZZ produced significant dose-dependent increases in the latency time in the hot-plate test with respect to controls, and in the formalin-induced paw licking test, the EOZZ also significantly reduced the painful stimulus in both neurogenic and inflammatory phase of the test. In addition, the antinociceptive effect of the EOZZ in the formalin-induced paw licking test as well as hot-plate test was reversed by the nonselective opioid receptor antagonist, naloxone suggesting that the opioid system was involved in its analgesic mechanism of action. On the basis of these data, we concluded that the EOZZ possessed both central and peripheral antinociceptive activities which justifying its popular folkloric use to relieve some pain conditions.
Flavonoid combinations cause synergistic inhibition of proinflammatory mediator secretion from lipopolysaccharide-induced RAW 264.7 cells

Harasstani OA, Moin S, Tham CL, Liew CY, Ismail N, Rajajendram R, et al.

Inflamm Res, 2010 Sep;59(9):711-21.
PMID: 20221843 DOI: 10.1007/s00011-010-0182-8

OBJECTIVES: We evaluated several flavonoid combinations for synergy in the inhibition of proinflammatory mediator synthesis in the RAW 264.7 cellular model of inflammation.
METHODS: The inhibitory effect of chrysin, kaempferol, morin, silibinin, quercetin, diosmin and hesperidin upon nitric oxide (NO), prostaglandin E(2) (PGE(2)) and tumour necrosis factor-alpha (TNF-alpha) secretion from the LPS-induced RAW 264.7 monocytic macrophage was assessed and IC(50) values obtained. Flavonoids that showed reasonable inhibitory effects in at least two out of the three assays were combined in a series of fixed IC(50) ratios and reassessed for inhibition of NO, PGE(2) and TNF-alpha. Dose-response curves were generated and interactions were analysed using isobolographic analysis.
RESULTS: The experiments showed that only chrysin, kaempferol, morin, and silibinin were potent enough to produce dose-response effects upon at least two out of the three mediators assayed. Combinations of these four flavonoids showed that several combinations afforded highly significant synergistic effects.
CONCLUSIONS: Some flavonoids are synergistic in their anti-inflammatory effects when combined. In particular chrysin and kaempferol significantly synergised in their inhibitory effect upon NO, PGE(2) and TNF-alpha secretion. These findings open further avenues of research into combinatorial therapeutics of inflammatory-related diseases and the pharmacology of flavonoid synergy.