Indian J Exp Biol

JUNE 2002

CODEN: IJEB (A6)  40(6)  633-748  (2002)

ISSN: 0019-5189

 

 

 

Indian Journal of Experimental Biology

http : // www.niscom.res.in; http : // www.bioline.org.br/

 

VOLUME 40

NUMBER 6

JUNE 2002

 

CONTENTS

Symposium in Print on Free Radical Biology

 

Immune system and antioxidants, especially those derived from Indian medicinal plants

T P A Devasagayam & K B Sainis

 

639

 

 

 

 

Oxidative stress and experimental carcinogenesis

Mohammad Athar

656

 

 

 

 

Melatonin oxidative stress and neurodegenerative diseases

Venkatramanujan Srinivasan

668

 

 

 

 

Biological significance of singlet oxygen

Thomas P A Devasagayam & Jayashree P Kamat

680

 

 

 

 

Involvement of reactive oxygen species in gastric ulceration: Protection by melatonin

Debashis Bandyopadhyay, Kaushik Biswas, Mrinalini Bhattacharyya,

Russel J Reiter & Ranajit K Banerjee

693

 

 

 

 

Inevitable glutathione, then and now

S V S Rana, Tanu Allen & Rajul Singh

706

 

 

 

 

Mechanistic pathways of antioxidant cytoprotection by a novel IH636 grape seed proanthocyanidin extract

Debasis Bagchi, Sidhartha D. Ray, Manashi Bagchi, Harry G. Preuss &

Sidney J. Stohs

 

717

 

 

 

 

Free radical scavenging and metal chelation by Tinospora cordifolia, a possible role in radioprotection

H C Goel, I Prem Kumar & S V S Rana

 

727

 

 

 

 

Effect of antioxidants (vitamin C, E and turmeric extract) on methimazole induced

hypothyroidism in rats

Usha R Deshpande, Lebana J Joseph, Uma N Patwardhan & Aban M Samuel

 

735

 

 

 

 

Caffeine, quercetin and alizarin stimulate the exhalation of metabolic products of

[14C]-N-nitrosodiethylamine in mice

K L Khanduja, R K Sangari & A Bhardwaj

 

739

 

 

 

 

Report

 

 

National Seminar on Biotechnology ¾ Challenges and Prospects

K Rajendra & M Anuradha

745

 

 

 

 

Indian Journal of Experimental Biology

Vol. 40, June 2002, pp. 639-655

 

Immune system and antioxidants, especially those derived from
Indian medicinal plants

T P A Devasagayam & K B Sainis

 

During the functioning of the immune system, such as in phagocytosis, reactive oxygen and nitrogen species are generated. If they are left unchecked they can affect the components of the immune system by inducing oxidative damage. This is more so in the elderly or during inflammation where there is excess generation of these reactive species than can be taken care of by the defenses in the form of antioxidants. Dietary supplementation with antioxidants may greatly help in such conditions. There are some indications of possible benefits of antioxidant supplementation. Natural compounds from medicinal plants having antioxidant and immunomodulatory activities have potential as therapeutic agents in this regard. Indian medicinal plants with these activities have been identified and their antioxidant and immunomodulatory effects reviewed. The possible future prospects in this regard are also outlined.

 

Indian Journal of Experimental Biology

Vol. 40, June 2002, pp. 656-667

 

Oxidative stress and experimental carcinogenesis

Mohammad Athar

 

The focus of this review is to provide state-of-the-art knowledge on the involvement of  oxygen free radicals (OFR) in carcinogenesis with a particular reference to skin model system as the process of cancer development is best understood in this organ. However, a brief description of the role of OFR in other organs is also provided. The term OFR refers to forms of oxygen exhibiting high reactivity and having at least one unpaired electron. The role of OFR in different stages of carcinogenesis such as initiation, promotion and progression is described. Out of many mechanisms described for the chemical initiation of tumorigenesis, a number of them may involve free radicals in the cascade of reactions. Evidences that support the involvement of free radicals in tumor promotion include (i)  a number of free radical-generating compounds are found to be tumor promoters in various animal model systems, (ii) ROS generating systems can mimic the biochemical action of tumor promoters, (iii) some tumor promoters stimulate the production of ROS, (iv) tumor promoters modulate the cellular antioxidant defense systems, and (v) free radical scavengers, detoxifiers and antioxidants inhibit the process of tumor promotion. The role of ROS in the progression stage of carcinogenesis is evident from the fact that a number of different free radical generating compounds enhance the malignant conversion of benign papillomas into carcinoma and their effectiveness may be related to the type of radicals produced into the biological system.

Indian Journal of Experimental Biology

Vol. 40, June 2002, pp. 668-679

 

Melatonin oxidative stress and neurodegenerative diseases

Venkatramanujan Srinivasan

 

Oxidative Stress is implicated as one of the primary factors that contribute to the development of neurodegenerative diseases like Alzheimer’s Disease, Parkinsonism and neurological conditions like epileptic seizures, stroke, brain damage, neurotrauma etc. The increased formation and release of oxygen free radicals coupled with the rather low antioxidative potential of the central nervous system are the major reasons that account for the enhanced oxidative stress seen in neuronal cells. In addition to this, brain is also enriched with polyunsaturated fatty acids that render neuronal cells easily vulnerable to oxidative attack. The fact that there is increased incidence of neurodegenerative disorders in aged individuals, has prompted many investigators to search for a common factor whose progressive decline with increase in age could account for increased oxidative stress resulting in senescence and age associated degenerative diseases. Since melatonin, the hormone secreted from the pineal gland has a remarkable anti-oxidant property and whose rate of production declines with increase in age, has prompted many to suggest that this hormone plays a crucial role in the genesis of neurodegenerative diseases. Melatonin cannot only scavenges oxygen free radicals like super oxide radical (O), hydroxyl radical (.OH), peroxyl radical (LOO.) and peroxynitrite anion (ONOO-), but can also enhance the antioxidative potential of the cell by stimulating the synthesis of antioxidative enzymes like super oxide dismutase (SOD), glutathione peroxidase (GPX), and also the enzymes that are involved in the synthesis of glutathione. In many instances, melatonin increases the expression of m RNA’s of the antioxidative enzymes. Melatonin administration has been shown to be effective in counteracting the neurodegenerative conditions both in experimental models of neurodegenerative diseases and in patients suffering from such diseases. A disturbance of melatonin rhythm and secretion also has been noted in patients suffering from certain neurodegenerative diseases. From all these, it is evident that melatonin has a neuroprotective role.

 

Indian Journal of Experimental Biology

Vol. 40, June 2002, pp. 680-692

 

Biological significance of singlet oxygen

Thomas P A, Devasagayam & Jayashree P Kamat

 

The biological significance of singlet oxygen (1O2), an electronically excited species of oxygen, has been realized only in the last two decades. This was mainly due to the lack of proper methodology to generate this reactive oxygen species (ROS) in pure form and its reactions with biological molecules. Recent studies, using newly developed detection methods, show that 1O2 being generated in many biological systems, can significantly and quite often adversely alter several crucial biomolecules including DNA, proteins and lipids with undesirable consequences including cytotoxicity and/or disesase development. The reactions of 1O2 with the biological molecules are rather specific, as compared to other ROS. There are various compounds, mainly derived from natural sources that offer protection against damage induced by 1O2. Among the antioxidants carotenoids are the most effective singlet oxygen quenchers followed by tocopherols and others. The same reactive species if generated specifically in diseased states such as cancer can lead to the cure of the disease, and this principle is utilized in the newly developing modality of cancer treatment namely photodynamic therapy. Singlet oxygen, in low concentrations can also act as signaling molecule with several biological implications. This review clearly brings out the biological significance of 1O2.

 

 

Indian Journal of Experimental Biology

Vol. 40, June 2002, pp. 693-705

 

 

Involvement of reactive oxygen species in gastric ulceration:
Protection by melatonin

Debashis Bandyopadhyay, Kaushik Biswas, Mrinalini Bhattacharyya, Russel J Reiter & Ranajit K Banerjee

 

Uncontrolled hydrochloric acid secretion and ulceration in the stomach due to various factors are serious global problems today. Although the mechanism of acid secretion from the parietal cell is now fairly known, the mechanism of gastric ulceration is still not clear today. Among various causes of gastric ulceration, lesions caused by stress, alcohol consumption, Helicobacter pylori infection and use of nonsteroidal antiinflammatory drugs have been shown to be mediated largely through the generation of reactive oxygen species especially hydroxyl radical (·OH). A number of excellent drugs have been proved useful in controlling hyperacidity and ulceration but their long term uses are not devoid of disturbing side-effects. Hence, the search is still on to find out a compound possessing antisecretory, antiulcer and antioxidant properties which will serve as a powerful therapeutic agent to cure gastric hyperacidity and ulcer. This article describes the role of reactive oxygen species in gastric ulceration, drugs controlling them with their merits and demerits and, the role of melatonin, a pineal hormone in protecting the gastric lesions with a final commentary on how melatonin research with respect to gastric pathophysiology can be taken forward with a view to projecting this indole as a promising therapeutic agent to control gastric ulceration in humans.

 

Indian Journal of Experimental Biology

Vol. 40, June 2002, pp. 706-716

 

Inevitable glutathione, then and now

S V S Rana, Tanu Allen & Rajul Singh

Glutathione a predominant tripeptide thiol compound of many prokaryotes and eukaryotes, is synthesized from its precursor amino acids eg. γ-glutamate, cysteine and glycine. It is mainly involved in detoxication mechanisms through conjugation reactions. Other functions include thiol transfer, destruction of free radicals and metabolism of various exogenous and endogenous compounds. It becomes mandatory for a cell to manage high concentration of intracellular GSH to protect itself from chemical/dug abuse. Glutathione dependent enzymes viz: glutathione-S-transferases, glutathione peroxidase, glutathione reductase and γ-glutamate transpeptidase facilitate protective manifestations. Liver serves as a glutathione-generating factor which supplies the kidney and intestine with other constituents of glutathione resynthesis. The principal mechanism of hepatocyte glutathione turnover appears to be cellular efflux. Kidney too plays an important role in organismic GSH homeostasis. Role of GSH in organs like lung, intestine and brain has recently been described. GSH involvement in programmed cell death has also been indicated. Immense interest makes the then “thee glutathione” as “inevitable glutathione”. This article describes the role of this vital molecule in cell physiology and detoxication mechanisms in particular.

 

Indian Journal of Experimental Biology

Vol. 40, June 2002, pp. 717-726

 

Mechanistic pathways of antioxidant cytoprotection by a novel IH636 grape seed proanthocyanidin extract

Debasis Bagchi, Sidhartha D. Ray, Manashi Bagchi, Harry G. Preuss & Sidney J. Stohs

 

To understand the bioavailability and mechanistic pathways of cytoprotection by IH636 grape seed proanthocyanidin extract (GSPE, commercially known as ActiVin) a series of in vitro and in vivo studies were conducted. Comparative protective abilities of GSPE, and vitamins C and E, singly and in combination, were assessed against smokeless tobacco extract (STE)-induced oxidative stress, DNA fragmentation and apoptotic cell death in a primary culture of normal human oral keratinocytes. GSPE protected against STE-induced oxidative stress, DNA damage and apoptotic cell death, and provided better protection as compared to vitamins C and E, singly and in combination. The bioavailability and protective ability of GSPE were examined against acetaminophen (AP)-induced hepato- and nephrotoxicity, amiodarone (AM)-induced lung toxicity, doxorubicin (DX)-induced cardiotoxicity and dimethylnitrosamine (DM)-induced spleenotoxicity in mice. GSPE-fed animals were compared with GSPE-untreated mice to evaluate the protective ability of GSPE against these structurally diverse drugs/chemicals. Serum chemistry changes, histopathology and DNA damage were evaluated. Results indicate that GSPE preexposure prior to the drugs/chemicals such as AP, AM, DX or DM treatment, provided near complete protection in terms of serum chemistry changes and inhibition of both forms of cell death, e.g., apoptosis and necrosis. DNA damage in various tissues triggered by these agents was significantly reduced in GSPE-fed animals. Histopathological examination of multiple target organs provided similar data. The results suggest that GSPE exposure is bioavailable and provides significant multiorgan protection against structurally diverse drug- and chemical-induced toxic assaults. Further, these studies exhibited a series of mechanistic information including free radical scavenging ability, anti-endonucleolytic activity, cytochrome P450 2E1 inhibitory activity, anti-necrotic, anti-apoptotic and anti-carcinogenic activities, modulatory effects on antioxidative and apoptotic regulatory genes such as Bcl2, c-myc and p53, which may be responsible for the novel chemoprotective properties exhibited by GSPE.

 

Indian Journal of Experimental Biology

Vol. 40, June 2002, pp. 727-734

 

Free radical scavenging and metal chelation by Tinospora cordifolia, a possible role in radioprotection

H C Goel & I Prem Kumar

and

S V S Rana

Aqueous extract of T. cordifolia inhibited Fenton (FeSO4) reaction and radiation mediated 2-deoxyribose degradation in a dose dependent fashion with an IC50 value of 700 mg/ml for both Fenton and radiation mediated 2-DR degradation. Similarly, it showed a moderate but dose dependent inhibition of chemically generated superoxide anion at 500 mg/ml concentration and above with an IC50 value of 2000 mg/ml. Aqueous extract inhibited the formation of Fe2+-bipiridyl complex and formation of comet tail by chelating Fe2+ ions in a dose dependent manner with an IC50 value of 150 mg/ml for Fe2+-bipirydyl formation and maximally 200 mg/ml for comet tail formation, respectively. The extract inhibited ferrous sulphate mediated lipid peroxidation in a dose-dependent manner with an IC50 value of 1300 mg/ml and maximally (70%) at 2000 mg/ml. The results reveal that the direct and indirect antioxidant actions of T. cordifolia probably act in corroboration to manifest the overall radioprotective effects.

 

Indian Journal of Experimental Biology

Vol. 40, June 2002, pp. 735-738

 

Effect of antioxidants (vitamin C, E and turmeric extract) on methimazole induced hypothyroidism in rats

Usha R Deshpande, Lebana J Joseph, Uma N Patwardhan & Aban M Samuel

 

Received 6 June 2001; revised 22 January 2002

 

The study was to investigate the protective effect of antioxidants against methimazole (MMI) induced hypothyroidism in rats. Male Wistar rats were fed MMI, MMI plus vitamin C, MMI plus vitamin E and MMI plus turmeric extract (TE) supplemented diet. At the end of the experiments, thyroid weights, thyroxine ( T4) , triiodothyronine (T3) and cholesterol levels were determined. It was observed that MMI treated rats showed increase in thyroid weights , very low levels of circulating T4, T3 and increased levels of total cholesterol as compared to controls (P< 0.001) . However , rats which received Vit. C, Vit. E or TE along with MMI showed reduced weights ( 38-55 % less ) in thyroid glands (P < 0.01 ) , less suppressed T4 and T3 levels ( 2-6 % and 7-35% respectively ) and less increase in total cholesterol levels ( 19-52 % ) which are statistically significant.The data suggest the positive effect of antioxidants on thyroid gland which could be due to direct involvement of antioxidants on thyroid gland.

 

 

Indian Journal of Experimental Biology

Vol. 40, June 2002, pp. 739-744

 

 

Caffeine, quercetin and alizarin stimulate the exhalation of metabolic products of [14C]-N-nitrosodiethylamine in mice

K L Khanduja, R K Sangari & A Bhardwaj

 

Received 17 April 2001; revised 1 March 2002

Naturally occurring plant products belonging to different chemical classes namely alizarin, an anthraquinone, caffeine, a methylxanthine derivative and quercetin, a flavonol were studied for their effect on elimination of metabolites of [14C]-N-nitrosodiethylamine (14C-NDEA) through respiration in mice. Treatment with caffeine, quercetin and alizarin at doses of 200, 9 and 9 µg/ml respectively, in drinking water enhanced the exhalation of 14CO2, one of the major end products of NDEA metabolism. Radioactive CO2 exhaled in 60 min increased by 2, 1.61 and 1.4-folds in animals treated with caffeine, quercetin and alizarin for 8 weeks respectively. This increase in exhalation in caffeine-treated animals was achieved even in 2 weeks. These compounds had no adverse effects on the absorption of radioactive NDEA from the gut of the animals as shape and time of 14CO2 peak was similar in ip and orally administered [14C-NDEA]. Increased detoxification/elimination of the carcinogen could be one of the mechanisms for the anticarcinogenic properties of these phytochemicals in lung tumorigenesis induced by orally administered NDEA.

 

Indian Journal of Experimental Biology

Vol. 40, June 2002, pp. 745-746

 

Report

National Seminar on Biotechnology ¾ Challenges and Prospects

K Rajendra & M Anuradha