No abstract

One of the most intriguing phenomenon observed during lead toxicity has been attributed to lead-induced oxidative stress. The combined effect of DL-a-lipoic acid (LA) and meso 2,3-dimercaptosuccinic acid (DMSA) on lead-induced alterations in selected parameters, which are indicators of oxidative stress in erythrocytes, have been studied. Lead acetate (Pb, 0.2%) was administered in drinking water for 5 weeks to induce toxicity. LA (25 mg/ kg body weight per day i.p.) and DMSA (20 mg/kg body weight per day i.p.) were administered individually and also in combination during week 6. Clinical evidence of toxic exposure was evident from the elevated blood lead levels (BPb) along with lowered levels of haemoglobin (Hb) and haematocrit (Ht). Lead-exposed animals showed enhanced membrane lipid peroxidation (LPO) in the erythrocytes. Damage to the erythrocyte membrane was evident from the decline in the activities of the trans-membrane enzymes, viz., Na1, K1 ATPase, Ca21 ATPase and Mg21 ATPase. Lead-exposed rats also suffered an onslaught on the antioxidant defence system witnessed by lowered activities of catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx) and reduced glutathione (GSH). Serum glutamic-oxoloacetic transaminase (SGOT) and serum glutamic-pyruvic transaminase (SGPT) were also elevated in lead-exposed rats. Treatment with either LA or DMSA reversed the lead-induced biochemical disturbances encountered by the erythrocytes, but combined treatment with LA and DMSA was very effective in mitigating all the parameters indicative of oxidative stress.

The deleterious effect of lead has been attributed to lead-induced oxidative stress with the consequence of lipid peroxidation. The present study was designed to investigate the combined effect of DL-alpha-lipoic acid (LA) and meso-2,3-dimercaptosuccinic acid (DMSA) on lead-induced peroxidative damages in rat kidney. The increase in peroxidated lipids in lead-poisoned rats was accompanied by alterations in antioxidant defence systems. Lead acetate (Pb, 0.2%) was administered in drinking water for 5 weeks to induce lead toxicity. LA (25 mg/kg body weight per day i.p.) and DMSA (20 mg/kg body weight per day i.p.) were administered individually and also in combination during the sixth week. Nephrotoxic damage was evident from decreases in the activities of gamma-glutamyl transferase and N-acetyl beta- D-glucosaminidase, which were reversed upon combined treatment with LA and DMSA. Rats subjected to lead intoxication showed a decline in the thiol capacity of the cell, accompanied by high malondialdehyde levels along with lowered activities of catalase, superoxide dismutase, glutathione peroxidase and glutathione metabolizing enzymes (glutathione reductase, glucose-6-phosphate dehydrogenase, glutathione- S-transferase). Supplementation with LA as a sole agent showed considerable changes over oxidative stress parameters. The study has highlighted the combined effect of both drugs as being more effective in reversing oxidative damage by bringing about an improvement in the reductive status of the cell.

One of the most intriguing phenomena observed during adriamycin (ADR) toxicity has been attributed to ADR-induced oxidative stress. The study was aimed to assess the protective effect of lipoic acid (LA) against ADR induced damage to erythrocytes. Male albino rats (Wistar strain) were subjected to ADR (1 mg/kg body weight/day i.v.) once a week for a period of 12 weeks. Haematological indices like haemoglobin levels (Hb) and haematocrit (Ht) were also lowered along with a marked increase in the activities of serum glutamate pyruvate transaminase (SGPT) and serum glutamate oxaloacetate transaminase (SGOT). These rats demonstrated enhanced erythrocyte membrane lipid peroxidation (LPO) and an onslaught in the antioxidant defence armoury, witnessed by lowered activities of superoxide dismutase (SOD), glutathione peroxidase (GPx), vitamin A, vitamin C and vitamin E. Rats administered with ADR showed a marked decline in the activities of membrane-bound ATPases. Abnormal LPO and decreased deformability led to increased osmotic fragility of the red blood cells. Pretreatment with LA (35 mg/kg body weight/day i.p.) 24 hours prior to the administration of ADR once a week for a period of 12 weeks was effective in counteracting these biochemical disturbances, thereby minimizing the toxic side effects of ADR.

This study has highlighted the beneficial effects of LA pretreatment in reversing the damages caused by ADR, by bringing about an improvement in the reductive status of the cell.

No abstract

BackgroundFatigue in rheumatoid arthritis (RA) is common, overwhelming and plays a key role in patients’ perception of the disease and strongly influences global assessment [1]. While fatigue in RA has no internationally accepted definition, it is multidimensional and has an inconsistent association with disease activity in different populations with very few studies from India [2, 3].ObjectivesTo determine the relationship between fatigue as measured by Patient-Reported Outcomes Measurement Information System (PROMIS) fatigue raw score with disease activity in patients with RA. To determine the predictors of fatigue in patients with RA.MethodsA longitudinal study was conducted from January 2021 to December 2022 after Ethics Committee approval in patients with RA enrolled at our rheumatology clinic providing care to >450 patients with RA, in a tertiary care hospital. Fatigue (PROMIS Fatigue-short form 7a), patient assessment of global disease activity (PtGA), Disease Activity Score (DAS28), and Clinical Disease Activity Index (CDAI) were measured. Serum samples for interleukin-6 (IL-6), and tumor necrosis factor alpha (TNF-α) were collected and stored at -800C. Relationship of fatigue was examined with age, hemoglobin, serum vitamin D3, TNF-α, and IL-6 using Spearman correlation coefficient. A Receiver Operating Characteristic (ROC) curve was constructed to determine the optimal PROMIS cut-off for defining PtGA >2. Binary logistic regression analysis was used to assess predictors fatigue.ResultsOne hundred and fifty-four patients were enrolled, of whom 133 (86.3%) were females, 103 were reassessed at 6 months (85.4% females). All were on conventional disease-modifying antirheumatic drugs. Patients in remission using DAS28 were 9.7% (n = 15) and 52.4% (n = 54) and remission/low disease activity (LDA) based on CDAI <10 were 13.6% (n = 21) and 68.9% (n = 71) at enrolment and 6 months respectively. There was a significant reduction in median PROMIS at 6 months from 19(11) to 16(7) (p<0.0001). PROMIS was significantly lower in those with remission/LDA based on CDAI (p<0.0001) and DAS28 remission at enrolment and 6 months (p = 0.012 and 0.015 respectively). PROMIS >11 had 93.8% sensitivity and 78.6% specificity to predict PtGA >2 (AUC 0.92, 95% CI 0.81 - 1.00, P <0.0001) (Figure 1). PROMIS >11 was present in 89% at enrolment and 82.5% at 6 months. Age, hemoglobin, serum vitamin D3, TNF-α, and IL-6 had no correlation with fatigue. DAS28, CDAI, sleep (Pittsburgh Sleep Quality Index - PSQI), and depression (Patient Health Questionnaire - PHQ-9) were significant predictors of PROMIS >11 (Table 1).ConclusionFatigue is a significant problem in RA. A PROMIS score of 11 may be an acceptable cut-off for our population. Though fatigue improved with the treat-to-target approach, further studies are needed to determine if it is meaningful for patients. Along with disease activity, addressing sleep and depression is important in managing fatigue.Table 1.Predictors of fatigue (n= 154)PredictorsOdds ratio (95% CI)P valuePSQI2.31(1.45 - 3.69)<0.0001PHQ-94.38 (2.16 - 8.89)<0.0001CDAI1.26 (1.13 - 1.39)<0.0001DAS282.87 (1.72 - 4.79)<0.0001References[1]Beaumont JL, Davis ES, Curtis JR, Cella D, Yun H. Meaningful Change Thresholds for Patient-Reported Outcomes Measurement Information System (PROMIS) Fatigue and Pain Interference Scores in Patients With Rheumatoid Arthritis. J Rheumatol. 2021 Aug 1;48(8):1239–42.[2]Singh H, Arya S, Talapatra P, Lather K, Mathur R, Singhania A, et al. Assessment of fatigue in rheumatoid arthritis (by Functional Assessment of Chronic Illness Therapy-Fatigue score) and its relation to disease activity and anemia. J Clin Rheumatol Pract Rep Rheum Musculoskelet Dis. 2014 Mar;20(2):87–90.[3]Versteeg GA, ten Klooster PM, van de Laar MAFJ. Fatigue is associated with disease activity in some, but not all, patients living with rheumatoid arthritis: disentangling “between-person” and “within-person” associations. BMC Rheumatol. 2022 Jan 7;6:3.Disclosure of InterestsNone Declared.

No abstract