IN"! ERNM IONAL JOURNAL OF LEPROSY^ Volume 50, Number 4

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Effect of Dapsone on Blood Lactic andPyruvic Acids in Leprosy'

Surendra N. Sinha, Suresh C. Gupta, Ashok K. Bajaj,Navin P. Srivastava, and Triyugi N. Mehrotra 2

Lactic and pyruvic acids arc the twoprincipal products of carbohydrate metab-olism. Pyruvic acid is of major importancesince it is further metabolized and providesenergy for vital activities. The effect of lep-rosy on these important metabolites has notbeen well studied. Dapsone (DDS) is widelyused in the treatment of this disease. Sinceleprosy involves various organs and theirmetabolic processes, the present work wasundertaken to study the effect of leprosyand DDS therapy on the basal levels ofblood lactic and pyruvic acids.

MATERIALS AND METHODSEighty-seven cases of lepromatous (LL)

and 80 cases of tuberculoid (TT) leprosywere studied for basal levels of blood lacticand pyruvic acids. Out of 87 LL patients,19 were untreated and 68 had had treatmentwith DDS for different durations. Similarly,in the TT group, 24 cases were untreated and56 had had treatment. As controls, 30 appar-ently healthy subjects from the same socio-economic status were also studied.

Blood lactic acid was determined by thecolorimetric method of Barker and Sum-merson (') and pyruvic acid by the methodof Friedmann and Haugen ( 3). The bloodsamples were drawn under fasting condi-tions.

RESULTSLactic acid was found to be significantly

raised in untreated cases of lepromatous aswell as tuberculoid leprosy. The increase of

' Received for publication on 26 March 1982; ac-cepted for publication on 8 June 1982.

2 S. N. Sinha, Ph.D., D.Sc., Lecturer in ChemicalPathology; S. C. Gupta, M.D., F.R.C.P. (Edin.), Pro-fessor of Pathology; A. K. Bajaj, M.D., Reader in Skinand V.D.; N. P. Srivastava, M.B., B.S., Demonstratorin Pathology; T. N. Mehrotra, M.D., Ph.D. (Lond.),Professor and Head, Department of Pathology, M. L.N. Medical College, Allahabad (U.P.), India.

lactic acid in tuberculoid cases was foundto be relatively more than in lepromatouscases. In treated cases, lactic acid valuesshowed a further increasing trend with theduration of therapy in lepromatous casesbut not in tuberculoid cases (The Table).The differences in lactic acid levels be-tween untreated and treated cases of eachgroup were not statistically significant.

Pyruvic acid was also found to be raisedin untreated cases of both these forms ofleprosy. The increase was more marked inlepromatous leprosy and the values indi-cated a mild increase with the duration ofthe disease in this group. A further increasein pyruvic acid was found in both lep-romatous and tuberculoid cases treated withDDS, but the values showed an increasingtrend with the duration of therapy only inlepromatous cases.

DISCUSSIONLeprosy affects lactate and pyruvate me-

tabolism. The blood levels of both theseacids are significantly raised in untreatedcases of lepromatous as well as tuberculoidleprosy. An increasing trend with the du-ration of the disease was seen in the lep-romatous cases. Normally, in glycolysis,pyruvic acid is formed mainly under aero-bic conditions, and lactic acid under anaer-obic conditions. The simultaneous increaseof both the metabolites in the present studyindicates that the cause of their increase isindependent of each other. The increase oflactic acid seems to be due to cellular hy-poxia in leprosy. Interestingly, the increaseof lactic acid in untreated tuberculoid caseswas found to be slightly more than in un-treated lepromatous cases, although the lat-ter type of the disease is more severe andprogressive. The reason for this is not clear.The data seem to suggest that in tubercu-loid leprosy anaerobic conditions are moredominant. Lactic acid was also found to be

468

50, 4^Sinha, et al..: DDS and Blood Lactic and Pyruvic Acids^469

THE TABLE. Blood lactic acid and pyruvic acid in leprosy.

Group No. of cases Lactic acid(Mean ± S.D. mg percent)

Pyruvic acid(Mean ± S.D. mg percent)

Healthy controls 30 8.53^L.".^1.47 0.85 ± 0.14Lcpromatous

Untreated<2 yr 7 10.44 ± 1.66 3 1.15 ± 0.14"

2-4 yr 6 11.38 ±^1.63" 1.23 ± 0.09">4 yr 6 12.44 ±^1.19" 1.33 ± 0.10"Treated<2 yr 23 10.86 ±^1.63° 1.35 ± 0.26"

2-4 yr 19 11.81^± 2.0° 0.24°1.59±024°>4 yr 26 12.68 ±^1.85" 1.68 ± 0.28"

TuberculoidUntreated<2 yr It) 0.63"11.52±0.63" 1.00 ± 0.06"

2-4 yr 9 12.71^±^1.13" 1.05 ± 0.08">4 yr 5 13.64 ±^1.87" 1.08 ± 0.09"Treated<2 yr 24 11.75 ±^1.30" 1.12 ± 0.20"

2-4 yr 17 12.18 ±^1.79" 1.41^± 0.18">4 yr 15 12.41 ± 2.46" 1.42 ± 0.18 1'

p < 0.01, Student's t test, compared to healthy control subjects." p < 0.001, Student's t test, compared to healthy control subjects.

raised in treated cases of both forms ofleprosy. The differences observed betweenuntreated and treated cases of each groupwere not statistically significant, suggestingthat DDS therapy was not effective in con-trolling the conditions responsible for theabnormal increases in lactic acid in leprosy.

Pyruvic acid was also found to be signif-icantly raised in both forms of leprosy, al-though the increases were more marked inlepromatous cases. The higher bacterialloads and their metabolic activity in lep-romatous leprosy could perhaps be respon-sible for this difference. The significant in-crease of pyruvic acid is suggestive ofthiamine deficiency ( 2), but this cannot besaid with certainty unless thiamine is mea-sured directly. It is well known that in thia-mine deficiency, the conversion of pyruvicacid to acetyl coenzyme A is hampered, re-sulting in the accumulation of pyruvic acid.Moreover, pyruvate is also formed by othermetabolic pathways besides glycolysiswhich are concerned with the process ofgluconeogenesis, transamination, anddeamination. It is quite possible that thesemetabolic processes are also affected inleprosy, resulting in pyruvic acid.

A further increase of pyruvic acid was

observed in both forms of leprosy treatedwith DDS. The values showed an increas-ing trend with the duration of therapy inlepromatous cases. Bharadwaj, et al. ( 2) intheir study of the effect of DDS on bloodlactic and pyruvic acids in lepromatouscases, with and without neuritis, also ob-served increases in pyruvic acid after DDStherapy. These observations clearly showthat DDS brings about a derangement ofpyruvate metabolism. It is not clear wheth-er DDS creates a further deficiency of thia-mine or affects pyruvate balance in someother way. Williams and Bradley (') studiedthe enzymes of the glycolytic pathway, i.e.,glucose-6-phosphate dehydrogenase, phos-phofructokinase, pyruvate kinase and al-dolase, in guinea pigs on toxic doses of DDSand found the levels of these enzymes tobe within normal limits. These observationssuggest that the production of pyruvate wasnormal and the abnormal, increased levelsof pyruvate after DDS therapy could be ex-plained only if there occurred a disturbancebeyond pyruvate production. An elaboratestudy of the various related metabolic path-ways is obviously needed to understand theunderlying mechanism of the deranged py-ruvate metabolism caused by DDS.

470^ International Journal of Leprosy^ 1982

The clinical manifestations of the pro-gressive accumulation of lactic and pyruvicacids in leprosy patients are also not wellstudied. One of the effects may be the gen-eral weakness usually felt by leprosy pa-tients in spite of a normal diet. It may bethat pyruvate, which is normally metabo-lized and serves as a source of energy inthe body, is not being utilized at a normalrate in leprosy patients. It is also not clearwhether some of the reported DDS toxici-ties are caused by the drug itself or are theresult of the adverse effects of accumulatedlactic and pyruvic acids.

SUMMARYThe effect of leprosy and dapsone (DDS)

on the basal levels of blood lactic and py-ruvic acids has been studied. In untreatedtuberculoid and lepromatous leprosy pa-tients both of the acids were found to besignificantly raised. The rise in lactic acidwas relatively more in tuberculoid patients;whereas pyruvic was relatively more ele-vated in lepromatous cases. Both the acidsshowed a tendency to increase with the du-ration of the disease in lepromatous lepro-sy. Statistically no significant differenceswere observed in lactic acid levels betweenuntreated and treated cases of both formsof leprosy, suggesting that DDS was not ef-fective in controlling the conditions respon-sible for the increased lactic acid. On theother hand, pyruvic acid showed a furtherincrease in cases who were on DDS thera-py, particularly in lepromatous cases. Thisindicated that DDS affects pyruvic acid me-tabolism. Whether DDS disturbs the nor-mal degradative pathway of pyruvic acid oraffects pathways of pyruvic acid produc-tion is not clear.

RESUMENSe estudiO el efecto de la lepra y la dapsona (DDS)

sobre los niveles basales de los acidos lactic() yvico en sangre. Tanto en los pacientes tuberculoidescomo en los lepromatosos no tratados se encontraronniveles significativamente elevados de ambos acidos.Sin embargo, mientras que la elevaciOn del zicido lac-tic° fue relativamente mayor en los pacientes tuber-culoides, el acid° pirtivico estuvo mzis elevado en loslepromatosos. Ambos acidos mostraron una tendenciaa incrementar que fue paralela a la duraciOn de la en-fermedad cuando esta fue del tipo lepromatoso. No seencontraron diferencias significativas en los niveles de

acid() lactico entre los casos tratados y los no tratadosde ambos formas de lepra sugiriendo, que el DDS notuvo efecto en el control de las condiciones quc de-terminaron el increment° en zicido Por otro lado,el acido pirtivico mostro un mayor increment() en loscasos que estuvieron bajo terapia con DDS, particu-larmente en los casos lepromatosos. Esto indic() queel DDS afecta el metabolism° del acid° pirtivico. Noestzi claro si el 1)1)S altera el catabolism° o el anabo-lism° del acid° pirtivico.

RESUMEL'action de la lepre et de la dapsone (DDS) stir les

taux de base des acides lactique et pyruvique du sangont ete etudiees. Chez les malades atteints de leprelepromateuse tuberculoide non traitee, on a observeune augmentation significative des taux de run et I'autrede ces acides. L'augmentation du taux d'acide lactiqueetait relativement plus prononcee chez les malades tu-berculoides. Par contre, les taux d'acide pyruviqueetztient relativement plus Cleves dans les cas de leprelepromateuse. On a releve une tendance a une eleva-tion des taux des deux acides dans la lepre leproma-teuse, en association avec la duree de la maladie. Au-cline difference statistiquement significative n'a etcobservee dans les taux d'acide lactique chez les ma-lades traites et chez les malades non traites, tant dansla forme lepromateuse quc dans la forme tuberculoide,ce qui suggere que la dapsone est depourvue d'actionpour contailer les conditions qui determinent ('aug-mentation du taux d'acide lactique. Par ailleurs, l'acidepyruvique a montre une augmentation plus prononceedans les cas qui etaient sous traitement a la dapsone,et ceci particulierement dans les cas lepromateux. Cesresultats indiqucnt que la dapsone affecte le metabo-lisms de l'acide pyruvique. II nest cependant pas clairsi cette action est exercee par le truchement dunemodification dans les voles normales de degradationde l'acide pyruvique, ou d'une alteration des voles deproduction de cet acide.

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Chem. 138 (1941) 535. Cited by Varley, H. Prac-tical Clinical Biochemistry. 4th ed. India: ArnoldHeinemann Private Ltd., 1975, pp. 617-618.

2. BIIARADWAJ, V. P., SRID1ARAN, V., VENKATE-

SAN, K., RAN1U, G. and DESIKAN, K. V. Effect ofDDS therapy on blood pyruvate and lactate levelsin leprosy patients. Lepr. Rev. 51 (1980) 237-241.

3. FRIEDMANN, T. E. and HAuGEN, G. E. J. Biol.Chem. 147 (1943) 415. Cited by Wootton, I. D. P.Micro-analysis in Medical Biochemistry. 4th ed.,London: J. & A. Churchill, Ltd., 1964, pp. 227-228.

4. WILLIAMS, M. H. and BRADLEY, W. G. An as-sessment of dapsone toxicity in the guinea pig. Br.J. Dermatol. 86 (1972) 650-654.