Phytochemical screening of Alstonia scholaris leaf and bark extracts and their antimicrobial activities.

Alstonia sholaris is an evergreen tree commonly found in South East Asia. In traditional medicine pharmacological activities are attributed to the leaves and bark of this plant. The aim of this study is characterizing the chemicals present in A. sholaris leaves and bark extracts and study their antimicrobial activities. Solvent extractions with Soxhlet apparatus of leaves and bark were obtained using hexane, benzene, isopropanol, methanol, and water. The crude extracts were concentrated and screened for qualitative phytochemical analysis and thin layer chromatography, and the antibacterial, antifungal an antiviral activity of crude extracts were measured by in vitro methods. Isopropanol and methanol extracts showed significant antibacterial activity and it was more pronounced against Gram positive than against Gram negative bacteria. Hexane, benzene, isopropanol and methanol fractions of A. scholaris bark and leaf showed activity against Enterobacter cloacae. Isopropanol extract showed maximum activity against selected human pathogenic fungus. In conclusion, the leaves and bark of A. scholaris are rich in phytochemicals with antimicrobial activities against human pathogens, being the isopropanol fraction the one with the highest antibacterial, antifungal, antiviral and anti-mycobacterial activities.

Efectos de una dieta con alto contenido de grasas sobre parámetros alimentarios y tejido adiposo blanco visceral de ratas Sprague Dawley / Effects of a high fat diet on dietary parameters and visceral white adipose tissue of Sprague Dawley rats

El incremento en las cifras de obesidad se debe esencialmente a factores de carácter ambiental asociados al consumo de alimentos con alto contenido de grasas saturadas. El objetivo del trabajo fue evaluar el efecto de una dieta alta en grasas sobre parámetros alimentarios y tejido adiposo blanco visceral. Se utilizaron ratas macho Sprague Dawley (n=10), divididas en dos grupos experimentales, el grupo control recibió dieta convencional (DC) y el grupo experimental una dieta alta en grasas (HFD), durante 10 semanas. Se determinó peso corporal, ingesta alimentaria, conversión alimenticia y características de tejido adiposo. El análisis de datos se realizó utilizando software IBM SPSS versión 21; tras evaluación de la normalidad de los datos, se aplicaron pruebas paramétricas T para muestras independientes y ANOVA de dos vías para medidas repetidas en uno de los factores, con ajuste Bonferroni. Se observó que el promedio de peso fue mayor en los animales alimentados con HFD, sin diferencia estadística respecto a DC, no obstante, existen diferencias significativas en el peso de las ratas alimentadas con HFD en distintos tiempos del protocolo, específicamente semanas 1, 5 y 10 (p<0,001). La ingesta alimentaria fue mayor en los animales alimentados con DC (p<0,005), sin embargo el consumo de energía fue mayor en aquellos alimentados con HFD (p=0,016), lo que derivó en una mayor conversión alimenticia (p<0,005). El promedio de diámetro teórico calculado de los adipocitos es estadísticamente mayor en grupo HFD (p<0,005), lo que se relaciona a la hipertrofia clásica generada tras un período de alimentación con elevado contenido de grasas. Conclusión: El protocolo permite establecer que efectivamente, dado la mayor densidad energética, HFD induce hipertrofia de los adipocitos, proceso característico de la obesidad.

The continued increase in obesity statistics is the result of environmental factors associated with the consumption of foods high in saturated fat. The objective of the work was to evaluate the effect of a high fat diet on food parameters and visceral white adipose tissue. in Male Sprague Dawley rats (n = 10) were used, divided into two experimental groups, the control group received conventional diet (DC) and the experimental group a high fat diet (HFD), for 10 weeks. Body weight, food intake, food conversion and adipose tissue characteristics were determined. Data analysis was performed using IBM SPSS version 21 software; after evaluating the normality of the data, parametric T tests were applied for independent samples and two-way ANOVA for repeated measurements in one of the factors, with Bonferroni adjustment. It was observed that the average weight was higher in animals fed with HFD, without statistical difference with respect to DC, however, there were significant differences in the weight of rats fed with HFD at different times of the protocol, specifically weeks 1.5 and 10 (p <0.001). Food intake was higher in animals fed DC (p <0.005), however the energy consumption was higher in those fed with HFD (p=0.016), which resulted in a higher feed conversion (p <0.005). The average theoretical diameter calculated for adipocytes is statistically higher in the HFD group (p <0.005), which is related to the classical hypertrophy generated after a period of feeding with high fat content. In conclusion, the protocol allows us to establish that, given the higher energy density, HFD induces adipocyte hypertrophy, a characteristic in the obesity process.

Dehydroascorbic acid, the oxidized form of vitamin C, improves renal histology and function in old mice.

Oxidative stress and inflammation are crucial factors that increase with age. In the progression of multiple age-related diseases, antioxidants and bioactive compounds have been recognized as useful antiaging agents. Oxidized or reduced vitamin C exerts different actions on tissues and has different metabolism and uptake. In this study, we analyzed the antiaging effect of vitamin C, both oxidized and reduced forms, in renal aging using laser microdissection, quantitative reverse-transcription polymerase chain reaction, and immunohistochemical analyses. In the kidneys of old SAM mice (10 months of age), a model of accelerated senescence, vitamin C, especially in the oxidized form (dehydroascorbic acid [DHA]) improves renal histology and function. Serum creatinine levels and microalbuminuria also decrease after treatment with a decline in azotemia. In addition, sodium-vitamin C cotransporter isoform 1 levels, which were increased during aging, are normalized. In contrast, the pattern of glucose transporter 1 expression is not affected by aging or vitamin C treatment. We conclude that oxidized and reduced vitamin C are potent antiaging therapies and that DHA reverses the kidney damage observed in senescence-accelerated prone mouse 8 to a greater degree.

Plant-Derived Bioactives in Oral Mucosal Lesions: A Key Emphasis to Curcumin, Lycopene, Chamomile, Aloe vera, Green Tea and Coffee Properties.

Oral mucosal lesions have many etiologies, including viral or bacterial infections, local trauma or irritation, systemic disorders, and even excessive alcohol and tobacco consumption. Folk knowledge on medicinal plants and phytochemicals in the treatment of oral mucosal lesions has gained special attention among the scientific community. Thus, this review aims to provide a brief overview on the traditional knowledge of plants in the treatment of oral mucosal lesions. This review was carried out consulting reports between 2008 and 2018 of PubMed (Medline), Web of Science, Embase, Scopus, Cochrane Database, Science Direct, and Google Scholar. The chosen keywords were plant, phytochemical, oral mucosa, leukoplakia, oral lichen planus and oral health. A special emphasis was given to certain plants (e.g., chamomile, Aloe vera, green tea, and coffea) and plant-derived bioactives (e.g., curcumin, lycopene) with anti-oral mucosal lesion activity. Finally, preclinical (in vitro and in vivo) and clinical studies examining both the safety and efficacy of medicinal plants and their derived phytochemicals were also carefully addressed.

SVCT2 Expression and Function in Reactive Astrocytes Is a Common Event in Different Brain Pathologies.

Ascorbic acid (AA), the reduced form of vitamin C, acts as a neuroprotector by eliminating free radicals in the brain. Sodium/vitamin C co-transporter isoform 2 (SVCT2) mediates uptake of AA by neurons. It has been reported that SVCT2 mRNA is induced in astrocytes under ischemic damage, suggesting that its expression is enhanced in pathological conditions. However, it remains to be established if SVCT expression is altered in the presence of reactive astrogliosis generated by different brain pathologies. In the present work, we demonstrate that SVCT2 expression is increased in astrocytes present at sites of neuroinflammation induced by intracerebroventricular injection of a GFP-adenovirus or the microbial enzyme, neuraminidase. A similar result was observed at 5 and 10 days after damage in a model of traumatic injury and in the hippocampus and cerebral cortex in the in vivo kindling model of epilepsy. Furthermore, we defined that cortical astrocytes maintained in culture for long periods acquire markers of reactive gliosis and express SVCT2, in a similar way as previously observed in situ. Finally, by means of second harmonic generation and 2-photon fluorescence imaging, we analyzed brain necropsied material from patients with Alzheimer's disease (AD), which presented with an accumulation of amyloid plaques. Strikingly, although AD is characterized by focalized astrogliosis surrounding amyloid plaques, SVCT2 expression at the astroglial level was not detected. We conclude that SVCT2 is heterogeneously induced in reactive astrogliosis generated in different pathologies affecting the central nervous system (CNS).

Aging Selectively Modulates Vitamin C Transporter Expression Patterns in the Kidney.

In the kidney, vitamin C is reabsorbed from the glomerular ultrafiltrate by sodium-vitamin C cotransporter isoform 1 (SVCT1) located in the brush border membrane of the proximal tubules. Although we know that vitamin C levels decrease with age, the adaptive physiological mechanisms used by the kidney for vitamin C reabsorption during aging remain unknown. In this study, we used an animal model of accelerated senescence (SAMP8 mice) to define the morphological alterations and aging-induced changes in the expression of vitamin C transporters in renal tissue. Aging induced significant morphological changes, such as periglomerular lymphocytic infiltrate and glomerular congestion, in the kidneys of SAMP8 mice, although no increase in collagen deposits was observed using 2-photon microscopy analysis and second harmonic generation. The most characteristic histological alteration was the dilation of intracellular spaces in the basolateral region of proximal tubule epithelial cells. Furthermore, a combination of laser microdissection, qRT-PCR, and immunohistochemical analyses allowed us to determine that SVCT1 expression specifically increased in the proximal tubules from the outer strip of the outer medulla (segment S3) and cortex (segment S2) during aging and that these tubules also express GLUT1. We conclude that aging modulates vitamin C transporter expression and that renal over-expression of SVCT1 enhances vitamin C reabsorption in aged animals that may synthesize less vitamin C. J. Cell. Physiol. 232: 2418-2426, 2017. © 2016 Wiley Periodicals, Inc.

Potential Therapeutic Effects of Oleuropein Aglycone in Alzheimer's Disease.

Alzheimer's disease (AD) is an age-associated neurodegenerative amyloid disease and is considered a social and clinical problem the last decades, particularly in the Western countries. Amyloid diseases are characterized by the deposition of typically aggregated protein/peptides in tissues that are associated with brain degeneration and progressive cognitive impairment. The amyloid plaques and neurofibrillary tangles arise as a result of self-assembly into fibrillar material of amyloid-ß protein and hyperphosphorylated tau, respectively. Moreover, mounting evidence shows that oxidative and nitrosative stress plays a central role in the pathogenesis of neurodegenerative disorders such as AD. Oleuropein belongs to a specific group of polyphenols, the secoiridoids, which are abundant in Oleaceae. Oleuropein aglycone is abundant in extra virgin olive oil and it is generated as a product of a glucosidase released when olive fruits are crushed. This secoiridoid compound has radical-scavenging activity and antioxidative effects and it is considered a promising target to prevent amyloid toxicity as an inhibitor of the oligomer nucleation and growth. The neuroprotective and antioxidant effects of flavonoids have been found to strongly depend on their structure and functional groups. Oleuropein aglycone counteracts amyloid aggregation and toxicity affecting different pathways: amyloid precursor protein processing, amyloid-ß peptide and tau aggregation, autophagy impairment, and neuroinflammation. In the current work, available literature on oleuropein aglycone effects as antioxidant and inhibitor of amyloid deposits in AD is reviewed. Moreover, we discuss the chemistry, food sources and bioavailability of oleuropein aglycone.

Translation and validation of a Spanish version of the xerostomia inventory.

OBJECTIVE: The aim of this study was to validate a Spanish cross-cultural adaptation of the xerostomia inventory (XI). MATERIALS AND METHODS: The original English version of XI was translated into Spanish, cross-culturally adapted and field tested. The Spanish version of XI (XI-Sp) was tested with a sample of 41 patients with xerostomia. The reliability of the XI-Sp was determined through internal consistency and test-retest methods. The construct validity of XI-Sp was determined by means of correlation between XI-Sp scores and salivary flow measurements. RESULTS: Overall XI-Sp scores were 40.8 (SD = 10) for the first application and 40.2 (SD = 9.5) for the second. Cronbach's alpha value for the XI-Sp was 0.89 and 0.87, respectively, while interitem correlation averages were r = 0.44 and r = 0.39 for each application. Interitem correlation and corrected total was rc ≥0.30. The test-retest intraclass correlation coefficient value for the XI-Sp score was 0.59 and 0.91. Convergent validity for construct validity correlation with salivary flow showed a medium effect size (r2  = 0.10) for the first application but did not make a statistically significant prediction for the second (r2  = 0.7). CONCLUSIONS: This study provides evidence concerning the reliability of the XI-Sp, showing that it may be a useful tool for Spanish-speaking xerostomia patients for both clinical and epidemiologic research.

Protective actions of melatonin and growth hormone on the aged cardiovascular system.

Epidemiological studies indicate that certain aspects of lifestyle and genetics act as risk factors for a variety of cardiovascular disorders, including coronary disease, hypertension, heart failure and stroke. Aging, however, appears to be the major contributor for morbidity and mortality of the impaired cardiovascular system. Growth hormone (GH) and melatonin seem to prevent cardiac aging, as they contribute to the recovery of several physiological parameters affected by age. These hormones exhibit antioxidant properties and decrease oxidative stress and apoptosis. This paper summarizes a set of studies related to the potential role that therapy with GH and melatonin may play in the protection of the altered cardiac function due to aging, with a focus on experiments performed in our laboratory using the senescence-accelerated mouse as an aging model. In general, we observed significantly increased inflammation, oxidative stress and apoptosis markers in hearts from senescence-accelerated prone 10-month-old animals compared to 2-month-old controls, while anti-inflammatory and antiapoptotic markers as well as endothelial nitric oxide synthase were decreased. Senescence-accelerated resistant animals showed no significant changes with age. GH or melatonin treatment prevented the age-dependent cardiac alterations observed in the senescence-accelerated prone group. Combined administration of GH plus melatonin reduced the age-related changes in senescence-accelerated prone hearts in an additive fashion that was different to that displayed when administered alone. GH and melatonin may be potential agents for counteracting oxidative stress, apoptosis and inflammation in the aging heart.

Effect of chronic melatonin administration on several physiological parameters from old Wistar rats and SAMP8 mice.

UNLABELLED: The effect of melatonin administration on age-induced alterations in hepatocytes, central nervous system, immune system, and skin are reviewed. Twenty-two-month-old Wistar rats and SAMP8 (senescence prone) mice of 10 months of age were used as experimental models. Wistar rats were analyzed untreated or after the chronic administration of melatonin at a dose of 1 mg/kg/day in the drinking water for 10 weeks. At the end of the treatment period, the various parameters were investigated. Results were compared with those of 2-month-old controls. In hepatocytes, aging induced a significant increase in oxidative stress, inflammation, and apoptosis when compared to young animals. Melatonin administration significantly ameliorated all these age-related changes. The impairment of the cardiovascular system with aging appears to contribute to the increased morbidity and mortality of the aged subjects. The process was investigated in SAMP8 mice of 10 months of age. Melatonin was provided for 30 days at two different dosages (1 mg/kg/day and 10 mg/kg/day), also in the drinking water. After treatment, the expression of inflammatory mediators (tumor necrosis factor-α, interleukin 1 and 10, NFκBp50 and NFκBp52), apoptosis markers (BAD, BAX, and Bcl2), and parameters related to oxidative stress (heme oxygenases 1 and 2, endothelial and inducible nitric oxide synthases) were determined in the heart. Inflammation as well as oxidative stress and apoptosis markers were increased in old SAMP8 males, as compared to young controls. After treatment with melatonin, these age-altered parameters were partially reversed. The results suggest that oxidative stress and inflammation increase with aging and that chronic treatment with melatonin is able to reduce these parameters. In the skin, a reduction of epidermal thickness together with a marked increase of the hypodermis with great fat accumulation was observed in old rats, together with an increase in caspase 3, 8 of nucleosomes and LPO and a reduction in Bcl2 levels in the cultured keratinocytes. Melatonin treatment was able to reduce the fat content of the hypodermis and to increase Bcl2 and reduce nucleosomes, caspases, and LPO in keratinocytes. CONCLUSION: Melatonin administration exerts a beneficial effect against age-induced changes in several physiological parameters in Wistar rats and SAMP 8 mice.

Effect of growth hormone treatment on pancreatic inflammation, oxidative stress, and apoptosis related to aging in SAMP8 mice.

Aging is associated with an increase in inflammation, oxidative stress, and apoptosis. Furthermore, aging is accompanied by an alteration of the growth hormone (GH) -insulin-like growth factor-1 (IGF-1) axis. The aim of this study was to examine the regulation of these parameters in the pancreas of old mice and how GH treatment could affect this process. Male senescence-accelerated prone mice (SAMP8) and male senescence-accelerated resistant mice (SAMR1) 2 (young) and 10 months old were used (n = 40). Animals were divided into five experimental groups: 1 and 2, SAMP8/R1 young control; 3 and 4, SAMP8/R1 old control (untreated); and 5, SAMP8 old treated with GH. Physiologically equivalent doses of GH were administered for 1 month (2 mg subcutaneously [s.c.]/kg/day) and several parameters were analyzed. Aging was associated with increased inflammation, oxidative stress, and apoptosis (increased tumor necrosis factor-α [TNF-α], interleukin-ß [IL-ß], IL-6, monocyte chemoattractant protein-1 [MCP1], IL-2, heme oxygenase [HO-1], inducible nitric oxide synthase [iNOS], and nitric oxide metabolites [NOx]). The ratio of anti/pro apoptotic mRNA expression-B cell lymphoma 2 (Bcl-2) Bcl-2-associated X protein (BAX) + Bcl-xL/Bcl-2-associated death promoter (BAD)-was decreased during aging in SAMP8 mice. X-inhibitor of apoptosis (XIAP) was decreased during the aging process. Furthermore, no changes were observed in protein expression of nuclear factor-κB (NF-κB p65 and NF-κBp50-105. However, the protein expression of NF-κB p52-100 and inhibitor kappa B (IκB) alpha was increased with age in the pancreas of SAMP8 mice. On the other hand, the expression of IκB beta was decreased with aging. These results indicate that aging is associated with significant alterations in the relative expression of pancreatic genes involved in inflammation, oxidative stress, and apoptosis. According to our results, GH administration to old SAMP8 mice was able to improve pancreas from this parameters.

Beneficial effect of melatonin treatment on inflammation, apoptosis and oxidative stress on pancreas of a senescence accelerated mice model.

This study has investigated the effect of aging on parameters of inflammation, oxidative stress and apoptosis in pancreas obtained from two types of male mice models: senescence-accelerated prone (SAMP8) and resistant mice (SAMR1). Animals of 2 (young) and 10 months of age (old) were used (n = 64). The influence of the administration of melatonin in the drinking water for one month at two different dosages (1 and 10mg/(kg day) on old SAMP8 mice on these parameters was also studied. SAMP8 mice showed with age a significant increase in the relative expression of pancreatic genes involved in inflammation, oxidative stress and apoptosis. Furthermore the protein expression of several NFκB subunits was also enhanced. On the contrary aged SAMR1 mice did not show significant increases in these parameters. Melatonin administration to SAMP8 mice was able to reduce these age related alterations at the two used dosages.

Effect of a combined treatment with growth hormone and melatonin in the cardiological aging on male SAMP8 mice.

The effect of a chronic combined treatment with growth hormone (GH) plus melatonin (Mel) on different age-related processes in cytosolic and nuclear fractions of hearts from SAMP8 mice (2 and 10 months) has been investigated. The parameters studied have been messenger RNA expressions of IL-1, IL-10, NFkBp50, NFkBp52, TNFα, eNOS, iNOS, HO-1, HO-2, BAD, BAX, and Bcl2 and protein expressions of iNOS, eNOS, TNFα, IL-1, IL-10, NFkBp50, NFKbp52, and caspase activity (3 and 9). Our results supported the existence of a proapoptotic and oxidative status together with inflammatory processes in the heart of old mice, with increases of inflammatory cytokines, caspase activity, HO-1, BAX, NFkBp50, and NFkBp52 and decreases of eNOS and Bcl2. Also, we were able to observe the translocation of NFkB to nuclei. The combined treatment was able to partially reduce the incidence of these deleterious changes, showing differences with the separated treatments with GH and Mel as were investigated in previous articles from our group.

Growth hormone can improve insulin resistance and differentiation in pancreas of senescence accelerated prone male mice (SAMP8).

OBJECTIVE: The aim of the present study was to investigate the effect of aging on several parameters related to glucose metabolism, proliferation and differentiation in the pancreas and how GH administration to old SAMP8 mice could affect these parameters. MATERIALS AND METHODS: Pancreas samples were obtained from two types of male mice models: senescence-accelerated prone (SAMP8) and senescence-accelerated-resistant (SAMR1) mice SAMP8 and SAMR1 mice and the influence of exogenous administration of GH (2mgs.c./kg/day) on SAMP8 mice. RNA was isolated from pancreas samples of male mice using the kit RNeasy total RNA kit Ref. 50974104 (Qiagen). Insulin was measured in plasma by RIA kit and glucose was measured in plasma by an assay kit. RESULTS: Aging decreases the expression of differentiation in the pancreas of Pdx-1, FoxO 1 and FoxO 3A but not of Sirt 1 or of the expression of the proliferative genes PCNA and Sei1. The expression of glucagon and GLUT2 were increased with aging and no differences were observed in somatostatin and insulin expressions. Insulin levels in plasma were increased with aging in SAMP8 mice. IGF-1 expression was reduced with aging. The treatment with GH was able to increase the expression of Sirt 1, Pdx-1, FoxO 3A and IGF-1. On the other hand, the treatment decreased the expression of glucagon, GLUT2, somatostatin and insulin, furthermore GH was able to decrease the plasma levels of insulin in old male SAMP8 mice (p<0.0004). CONCLUSION: The present study has shown that aging is associated with significant alterations in the relative expression of pancreatic genes involved in insulin secretion as well as in the differentiation and in the intra islet glucose metabolism. According to our results, GH administration to old SAMP8 mice was able to improve the pancreatic function of the old SAMP8 mice and to decrease insulin and glucagon expressions in the pancreas improving instead insulin levels and glucose metabolism.

Melatonin improves inflammation processes in liver of senescence-accelerated prone male mice (SAMP8).

Aging is associated with an increase in oxidative stress and inflammation. The aim of this study was to investigate the effect of aging on various physiological parameters related to inflammation in livers obtained from two types of male mice models: Senescence-accelerated prone (SAMP8) and senescence-accelerated-resistant (SAMR1) mice, and to study the influence of the administration of melatonin (1mg/kg/day) for one month on old SAMP8 mice on these parameters. The parameters studied have been the mRNA expression of TNF-α, iNOS, IL-1ß, HO-1, HO-2, MCP1, NFkB1, NFkB2, NFkB protein or NKAP and IL-10. All have been measured by real-time reverse transcription polymerase chain reaction RT-PCR. Furthermore we analyzed the protein expression of TNF-α, iNOS, IL-1ß, HO-1, HO-2, and IL-10 by Western-blot. Aging increased oxidative stress and inflammation especially in the liver of SAMP8 mice. Treatment with melatonin decreased the mRNA expression of TNF-α, IL-1ß, HO (HO-1 and HO-2), iNOS, MCP1, NFκB1, NFκB2 and NKAP in old male mice. The protein expression of TNF-α, IL-1ß was also decreased and IL-10 increased with melatonin treatment and no significant differences were observed in the rest of parameters analyzed. The present study showed that aging was related to inflammation in livers obtained from old male senescence prone mice (SAMP8) and old male senescence resistant mice (SAMR1) being the alterations more evident in the former. Exogenous administration of melatonin was able to reduce inflammation.

Beneficial effects of melatonin on cardiological alterations in a murine model of accelerated aging.

This study investigated the effect of aging-related parameters such as inflammation, oxidative stress and cell death in the heart in an animal model of accelerated senescence and analyzed the effects of chronic administration of melatonin on these markers. Thirty male mice of senescence-accelerated prone (SAMP8) and 30 senescence-accelerated-resistant mice (SAMR1) at 2 and 10 months of age were used. Animals were divided into eight experimental groups, four from each strain: two young control groups, two old untreated control groups, and four melatonin-treated groups. Melatonin was provided at two different dosages (1 and 10 mg/kg/day) in the drinking water. After 30 days of treatment, the expression of inflammatory mediators (tumor necrosis factor-alpha, interleukin 1 and 10, NFkBp50 and NFkBp52), apoptosis markers (BAD, BAX and Bcl2) and parameters related to oxidative stress (heme oxygenases 1 and 2, endothelial and inducible nitric oxide synthases) were determined in the heart by real-time reverse transcription polymerase chain reaction (RT-PCR). Inflammation, as well as, oxidative stress and apoptosis markers was increased in old SAMP8 males, when compared to its young controls. SAMR1 mice showed significantly lower basal levels of the measured parameters and smaller increases with age or no increases at all. After treatment with melatonin, these age-altered parameters were partially reversed, especially in SAMP8 mice. The results suggest that oxidative stress and inflammation increase with aging and that chronic treatment with melatonin, a potent antioxidant, reduces these parameters. The effects were more marked in the SAMP8 animals.