MC1R and age heteroclassification of face phenotypes in the Rio Grande do Sul population.

BACKGROUND: Forensic DNA phenotyping (FDP) consists of the use of methodologies for predicting externally visible characteristics (EVCs) from the genetic material of biological samples found in crime scenes and has proven to be a promising tool in aiding human identification in police activities. Currently, methods based on multiplex assays and statistical models of prediction of EVCs related to hair, skin, and iris pigmentation using panels of SNP and INDEL biomarkers have already been developed and validated by the forensic scientific community. As well as traces of pigmentation, an individual's perceived age (PA) can also be considered an EVC and its estimation in unknown individuals can be useful for the progress of investigations. Liu and colleagues (2016) were pioneers in evidencing that, in addition to lifestyle and environmental factors, the presence of SNP and INDEL variants in the MC1R gene - which encodes a transmembrane receptor responsible for regulating melanin production - seems to contribute to an individual's PA. The group highlighted the association between these MC1R gene polymorphisms and the PA in the European population, where carriers of risk haplotypes appeared to be up to 2 years older in comparison to their chronological age (CA). PURPOSE: Understanding that genotype-phenotype relationships cannot be extrapolated between different population groups, this study aimed to test this hypothesis and verify the applicability of this variant panel in the Rio Grande do Sul admixed population. METHODS: Based on genomic data from a sample of 261 volunteers representative of gaucho population and using a multiple linear regression (MLR) model, our group was able to verify a significant association among nine intronic variants in loci adjacent to MC1R (e.g., AFG3L1P, TUBB3, FANCA) and facial age appearance, whose PA was defined after age heteroclassification of standard frontal face images through 11 assessors. RESULTS: Different from that observed in European populations, our results show that the presence of effect alleles (R) of the selected variants in our sample influenced both younger and older face phenotypes. The influence of each variant on PA is expressed as ß values. CONCLUSIONS: There are important molecular mechanisms behind the effects of MC1R locus on PA, and the genomic background of each population seems to be crucial to determine this influence.

MALA: Acidosis láctica asociado al uso de metformina, una revisión a propósito de casos clínicos

La metformina es el fármaco preferido en el manejo inicial de la diabetes mellitus tipo 2 (DMT2). Aunque se recomienda su uso ampliamente, se debe tener precaución al prescribirla a poblaciones susceptibles a condiciones de riesgo de hipoperfusión sistémica, ya que puede provocar acumulación en el organismo y alteraciones metabólicas que desemboquen en acidosis láctica asociada a metformina, una complicación grave que a menudo es subdiagnosticada. Con el propósito de promover un mejor conocimiento sobre este tema, la presente revisión se centra en el análisis de la clínica, fisiopatología, diagnóstico y manejo de la acidosis láctica asociada a metformina, prestando especial atención al manejo mediante terapias de reemplazo renal. El análisis se basará en la experiencia de una serie de casos de acidosis láctica asociada a metformina atendidos en un centro clínico hospitalario en Chile.

Metformin is the preferred medication for the initial management of type 2 diabetes mellitus (T2DM). Although its use is widely recommended, caution should be exercised when prescribing it to populations susceptible to systemic hypoperfusion conditions, as it can lead to accumulation in the body and metabolic disturbances that may result in metformin-associated lactic acidosis. This severe complication is often underdiagnosed. To promote a better understanding of this topic, the present review focuses on the analysis of the clinical, pathophysiological, diagnostic, and management aspects of metformin-associated lactic acidosis, with particular attention to management through renal replacement therapies. The analysis will be based on the experience of a series of cases of metformin-associated lactic acidosis treated at a hospital clinical center in Chile.

Medicina Espacial y Astronomía en Chile: Futuro esplendor

El cielo de Chile cuenta con las condiciones ideales para la astronomía a nivel mundial, lo que ha conllevado un desarrollo científico importante para el país en esta y otras áreas. En los próximos años varias misiones espaciales sucederán, siendo de importancia para su éxito la salud de los tripulantes. La medicina espacial se preocupa y estudia los cambios en la fisiología humana en el espacio, la que se ve alterada en su totalidad. Es fundamental el entendimiento de la patología en el ambiente espacial para el desarrollo de contramedidas para mitigar los diferentes riesgos, siendo uno de los principales la radiación espacial entre otros. El desarrollo de esta área de la medicina permitirá nuevos avances en la salud en la Tierra.

The sky of Chile has the ideal conditions for astronomy worldwide, which has led to crucial scientific development for the country in this and other areas. In the coming years, several space missions will occur, the crew members' health being essential for their success. Space medicine studies the changes in human physiology in space, which is entirely altered. It is essential to understand the pathology in the space environment to develop countermeasures to mitigate the different risks, one of the main ones being space radiation, among others. The development of this area of medicine will allow new advances in health on Earth.

Ancestry resolution of South Brazilians by forensic 165 ancestry-informative SNPs panel.

Forensic DNA phenotyping (FDP) includes biogeographic ancestry (BGA) inference and externally visible characteristics (EVCs) prediction directly from an evidential DNA sample as alternatives to provide valuable intelligence when conventional DNA profiling fails to achieve identification. In this context, the application of Massively Parallel Sequencing (MPS) methodologies, which enables simultaneous typing of multiple samples and hundreds of forensic markers, has been gradually implemented in forensic genetic casework. The Precision ID Ancestry Panel (Thermo Fisher Scientific, Waltham, USA) is a forensic multiplex assay consisting of 165 autosomal SNPs designed to provide biogeographic ancestry information. In this work, a sample of 250 individuals from Rio Grande do Sul (RS) State, southern Brazil, apportioned into four main population groups (African-, European-, Amerindian-, and Admixed-derived Gauchos), was evaluated with this panel, to assess the feasibility of this approach in a highly heterogeneous population. Forensic descriptive parameters estimated for each population group revealed that this panel has enough polymorphic and informative SNPs to be used as a supplementary instrument in forensic individual identification and kinship testing regardless of ethnicity. No statistically significant deviation from Hardy-Weinberg equilibrium was observed after Bonferroni correction. However, seven loci pairs displayed linkage disequilibrium in pairwise LD testing (p < 3.70 × 10-6). Interpopulation comparisons by FST analysis, MDS plot, and STRUCTURE analysis among the four RS population groups apart and along with 89 reference worldwide populations demonstrated that Admixed- and African-derived Gauchos present the highest levels of admixture and population stratification, whereas European- and Amerindian-derived exhibit a more homogeneous genetic conformation.

[MALA: Lactic acidosis associated with the use of metformin, review of clinical cases]. / MALA: Acidosis láctica asociado al uso de metformina, una revisión a propósito de casos clínicos.

Metformin is the preferred medication for the initial management of type 2 diabetes mellitus (T2DM). Although its use is widely recommended, caution should be exercised when prescribing it to populations susceptible to systemic hypoperfusion conditions, as it can lead to accumulation in the body and metabolic disturbances that may result in metformin-associated lactic acidosis. This severe complication is often underdiagnosed. To promote a better understanding of this topic, the present review focuses on the analysis of the clinical, pathophysiological, diagnostic, and management aspects of metformin-associated lactic acidosis, with particular attention to management through renal replacement therapies. The analysis will be based on the experience of a series of cases of metformin-associated lactic acidosis treated at a hospital clinical center in Chile.

[Advancing Space Medicine and Astronomy in Chile for Health on Earth]. / Medicina Espacial y Astronomía en Chile: Futuro esplendor.

The sky of Chile has the ideal conditions for astronomy worldwide, which has led to crucial scientific development for the country in this and other areas. In the coming years, several space missions will occur, the crew members' health being essential for their success. Space medicine studies the changes in human physiology in space, which is entirely altered. It is essential to understand the pathology in the space environment to develop countermeasures to mitigate the different risks, one of the main ones being space radiation, among others. The development of this area of medicine will allow new advances in health on Earth.

Acute kidney injury associated to sulfamethoxazole urine crystal: The importance of clinical suspicion.

Management of acute kidney injury (AKI) associated with drug-induced crystal nephropathy can be difficult, and timely diagnosis is critical to resolve this condition. We present the case of a 55-year-old woman with history of systemic lupus erythematosus (SLE), who, after treatment with trimethoprim/sulfamethoxazole (TMP/SMX) for suspected Pneumocystis jirovecii pneumonia, developed severe AKI. Automated urinary sediment initially reported hematuria, leukocyturia and "uric acid crystals". She did not have allergic symptoms, clinical manifestations of active SLE nor hyperuricemia. AKI persisted despite volume expansion with crystalloids. Due to SMX exposure, it was suspected that "uric acid crystals" could be in reality "SMX crystals", and were a possible cause of crystal nephropathy. TMP/SMX was withheld and urinary alkalization was performed, with subsequent resolution of AKI. SMX urine crystals were posteriorly confirmed by Fourier transform infrared spectroscopy.

[Severe metabolic disorder associated with an enterovesical fistula. Report of one case]. / Trastorno grave del medio interno por fístula enterovesical, a propósito de un caso clínico.

Enterovesical fistula (EVF) is a fistulous communication between the intestine and the bladder. It is uncommon and its classic clinical manifestations are the presence of pneumaturia, fecaluria, suprapubic pain and recurrent urinary infections. Surgical repair of EVF leads to rapid correction of both diarrhea and metabolic abnormalities. We report a 73-year-old diabetic woman with a neurogenic bladder secondary to a spine meningioma. She presented with diarrhea, vomiting, impaired consciousness and metabolic acidosis. She developed hypernatremia, hypokalemia, hypocalcemia, and hypophosphatemia, which were successfully corrected.

Trastorno grave del medio interno por fístula enterovesical, a propósito de un caso clínico / Severe metabolic disorder associated with an enterovesical fistula: report of one case

Enterovesical fistula (EVF) is a fistulous communication between the intestine and the bladder. It is uncommon and its classic clinical manifestations are the presence of pneumaturia, fecaluria, suprapubic pain and recurrent urinary infections. Surgical repair of EVF leads to rapid correction of both diarrhea and metabolic abnormalities. We report a 73-year-old diabetic woman with a neurogenic bladder secondary to a spine meningioma. She presented with diarrhea, vomiting, impaired consciousness and metabolic acidosis. She developed hypernatremia, hypokalemia, hypocalcemia, and hypophosphatemia, which were successfully corrected.

Haplotype distribution in a forensic full mtDNA genome database of admixed Southern Brazilians and its association with self-declared ancestry and pigmentation traits.

BACKGROUND: The advent of massively parallel sequencing (MPS) applications focused on the generation of forensic-quality full mitochondrial genome sequences led to a popularization of the technique on a global scale. However, the lack of forensic-graded population databases has refrained a wider adoption of full genome sequences as the industry standard, despite its better discrimination capacity of individual maternal lineages. PURPOSE: This work describes a forensic-oriented full mtDNA genome database comprised of 480 samples from a Southern Brazilian population. METHODS: A collection of mitochondrial sequences were obtained from low-pass, full genome DNA sequencing results. The complete sample set was evaluated regarding haplotype composition and distribution. Summary statistics and forensic parameters were calculated and are presented for the database, with detailed information concerning the impact of removing genetic information in the form of specific variants or increasingly larger genomic regions. Interpopulational analysis comparing haplotypical diversity in Brazilian and 26 worldwide populations was also performed. The association between mitochondrial genetic variability and phenotypic diversity was also evaluated in populations, with self-declared ancestry and three distinct phenotypic pigmentation traits (eyes, skin and hair colors) as parameters. RESULTS: The presented database can be used to evaluate mitochondrial-related genetic evidence, providing LR values of up to 20,465 for unobserved haplotypes. Haplotype distribution in Southern Brazil seems to be different than the remaining of the country, with a larger contribution of maternal lines with European origin. Despite association can be found between lighter and darker phenotypes or self-declared ancestry and haplotype distribution, prediction models cannot be reliably proposed due to the admixed nature of the Brazilian population. CONCLUSIONS: The proposed database provides a basis for statistical calculation and frequency estimation of full mitochondrial genomes, and can be part of an integrated, representative, national database comprising most of the genetic diversity of maternal lineages in the country.

Forensic characterization of 124 SNPs in the central Indian population using precision ID Identity Panel through next-generation sequencing.

With the advent of next-generation sequencing technology, SNP markers are being explored as a useful alternative to conventional capillary electrophoresis-based STR typing. Low mutation rate and short-sized amplicons are added advantages of SNP markers over the STRs. However, to achieve a sufficient level of discrimination among individuals, a higher number of SNPs need to be characterized simultaneously. Hence, the NGS technique is highly useful to analyze a sufficiently higher number of SNPs simultaneously. Though the technique is in its nascent stage, an attempt has been made to assess its usability in the central Indian population by analyzing 124 SNPs (90 autosomal and 34 Y-chromosome) in 95 individuals. Various quality parameters such as locus balance, locus strand balance, heterozygosity balance, and noise level showed a good quality sequence obtained from the Ion GeneStudio S5 instrument. Obtained frequency of SNP alleles ranged from 0.001 to 0.377 in autosomal SNPs. rs9951171 was found to be the most informative SNP in the studied population with the highest PD and lowest MP value. The cumulative MP of 90 SNPs was found to be 4.76698 × 10-37. Analysis of 34 Y-chromosome SNPs reveals 11 unique haplogroups in 54 male samples with R1a1 as the most frequent haplogroup found in 22.22% of samples. Interpopulation comparison by FST analysis, PCA plot, and STRUCTURE analysis showed genetic stratification of the studied population suggesting the utility of SNP markers present in the Precision ID Identity Panel for forensic demands of the Indian population.

[Acute phosphate nephropathy secondary to the use of oral sodium phosphate laxatives. Report of one case]. / Nefropatía aguda por fosfatos secundaria al uso de laxantes con fosfato de sodio: caso clínico-patológico.

Acute phosphate nephropathy (APN) is an acute renal failure secondary to the use of oral sodium phosphate (OSP) laxatives, with a high risk of progression to chronicity. We report a 60-year-old woman with mixed connective tissue disease whose serum creatinine increased up to 2.0 mg/dL in her regular control tests, without an evident causative factor. Kidney biopsy showed numerous intratubular calcium phosphate deposits, consistent with APN. She had a history of OSP laxative intake, and a sodium phosphate enema was used before a colonoscopy performed six months earlier. The temporal association between the use of OSP laxatives and acute kidney injury, should lead to the suspicion of APN. The urine sediment is generally normal or with mild to moderate proteinuria. The diagnosis is confirmed with a kidney biopsy. Until now, there is no specific treatment for APN, thus prevention is essential. In high-risk patients for developing APN, the administration of these laxatives should be avoided.

Comparison of machine learning techniques to handle imbalanced COVID-19 CBC datasets.

The Coronavirus pandemic caused by the novel SARS-CoV-2 has significantly impacted human health and the economy, especially in countries struggling with financial resources for medical testing and treatment, such as Brazil's case, the third most affected country by the pandemic. In this scenario, machine learning techniques have been heavily employed to analyze different types of medical data, and aid decision making, offering a low-cost alternative. Due to the urgency to fight the pandemic, a massive amount of works are applying machine learning approaches to clinical data, including complete blood count (CBC) tests, which are among the most widely available medical tests. In this work, we review the most employed machine learning classifiers for CBC data, together with popular sampling methods to deal with the class imbalance. Additionally, we describe and critically analyze three publicly available Brazilian COVID-19 CBC datasets and evaluate the performance of eight classifiers and five sampling techniques on the selected datasets. Our work provides a panorama of which classifier and sampling methods provide the best results for different relevant metrics and discuss their impact on future analyses. The metrics and algorithms are introduced in a way to aid newcomers to the field. Finally, the panorama discussed here can significantly benefit the comparison of the results of new ML algorithms.

Nefropatía aguda por fosfatos secundaria al uso de laxantes con fosfato de sodio: caso clínico-patológico / Acute phosphate nephropathy secondary to the use of oral sodium phosphate laxatives: report of one case

Acute phosphate nephropathy (APN) is an acute renal failure secondary to the use of oral sodium phosphate (OSP) laxatives, with a high risk of progression to chronicity. We report a 60-year-old woman with mixed connective tissue disease whose serum creatinine increased up to 2.0 mg/dL in her regular control tests, without an evident causative factor. Kidney biopsy showed numerous intratubular calcium phosphate deposits, consistent with APN. She had a history of OSP laxative intake, and a sodium phosphate enema was used before a colonoscopy performed six months earlier. The temporal association between the use of OSP laxatives and acute kidney injury, should lead to the suspicion of APN. The urine sediment is generally normal or with mild to moderate proteinuria. The diagnosis is confirmed with a kidney biopsy. Until now, there is no specific treatment for APN, thus prevention is essential. In high-risk patients for developing APN, the administration of these laxatives should be avoided.

Geographic origin determination of Brazilian Cannabis sativa L. (Marihuana) by multi-element concentration.

The Marihuana Polygon production of Cannabis sativa L. supplies the northeastern region of Brazil and represents 30% of the nation's market. The international trend of indoor cultivation is also occurring in Brazil, and the Brazilian Federal Police (BFP) has been increasing its apprehension of cannabis seeds sent by mail. The present work aims to assess the utility of the multi-element composition of different cannabis plant parts and soil samples where the plants were cultivated to determine their geographic origin. Statistical tools were applied to classification of marijuana samples from distinct geographic regions within northeastern Brazil, including indoor cultivated samples. The multi-element quantification was determined using inductively-coupled plasma - optical emission spectrometry (ICP-OES), and the data were compared by the Kruskal-Wallis H test, and subsequently, multiple discriminant analysis (MDA). The results of the multi-element concentration of cannabis plant samples were also subjected to a principal component analysis (PCA) and an orthogonal partial least squares discriminant analysis (OPLS-DA). The cannabis plant samples from the Marihuana Polygon could be clearly separated from those cultivated indoors, and the distance between them was detectable. The MDA revealed that phosphorus, calcium, magnesium, selenium, and arsenic concentrations were used as variables for this separation. Our results demonstrate that multi-element composition analysis can be used to indicate the origin or cultivation location of cannabis plants. Routine laboratory analyses consisting of multi-element composition combined with statistical analyses provide a reliable tool by which C. sativa movement, cultivation, and interdiction efforts in Brazil may be assessed.

Hemogram data as a tool for decision-making in COVID-19 management: applications to resource scarcity scenarios.

BACKGROUND: COVID-19 pandemics has challenged emergency response systems worldwide, with widespread reports of essential services breakdown and collapse of health care structure. A critical element involves essential workforce management since current protocols recommend release from duty for symptomatic individuals, including essential personnel. Testing capacity is also problematic in several countries, where diagnosis demand outnumbers available local testing capacity. PURPOSE: This work describes a machine learning model derived from hemogram exam data performed in symptomatic patients and how they can be used to predict qRT-PCR test results. METHODS: Hemogram exams data from 510 symptomatic patients (73 positives and 437 negatives) were used to model and predict qRT-PCR results through Naïve-Bayes algorithms. Different scarcity scenarios were simulated, including symptomatic essential workforce management and absence of diagnostic tests. Adjusts in assumed prior probabilities allow fine-tuning of the model, according to actual prediction context. RESULTS: Proposed models can predict COVID-19 qRT-PCR results in symptomatic individuals with high accuracy, sensitivity and specificity, yielding a 100% sensitivity and 22.6% specificity with a prior of 0.9999; 76.7% for both sensitivity and specificity with a prior of 0.2933; and 0% sensitivity and 100% specificity with a prior of 0.001. Regarding background scarcity context, resources allocation can be significantly improved when model-based patient selection is observed, compared to random choice. CONCLUSIONS: Machine learning models can be derived from widely available, quick, and inexpensive exam data in order to predict qRT-PCR results used in COVID-19 diagnosis. These models can be used to assist strategic decision-making in resource scarcity scenarios, including personnel shortage, lack of medical resources, and testing insufficiency.

Evaluation of two 13-loci STR multiplex system regarding identification and origin discrimination of Brazilian Cannabis sativa samples.

According to the Brazilian Federal Police (BFP), the Brazilian Cannabis sativa illicit market is mainly supplied by drugs originated from Paraguay and Northeastern Brazil (Marijuana Polygon region). These two known routes, the increasing indoor cultivations (supported by online market), and drugs from Uruguay are also in BFP's sight. Forensic tools to aid police intelligence were published in the past years. In genetics, microsatellites have gained attention due to their individualization capability. This study aims to evaluate the effectiveness and efficiency of two STR multiplex systems previously proposed in 94 Cannabis sativa samples seized in Brazil. Principal coordinate analyses (PCoA), forensic parameters, and genetic structure analysis were executed. Both panels were effective in individualizing and origin discriminating all samples, and the system proposed in 2015 demonstrated better results. For this marker set, the probability of identity for a random individual is approximately one in 65 billion; also, the PCoA shows a clear genetic distinction among samples according to its origin. Bayesian inference populational structure analysis indicated a significant genetic diversity among seizure groups, matching with its origin. Overall, the STR multiplex systems were able to achieve its purpose in individualizing and differentiating, according to geographic region, Brazilian Cannabis sp. samples.

Forensic characterization of Brazilian regional populations through massive parallel sequencing of 124 SNPs included in HID ion Ampliseq Identity Panel.

Use of Massive Parallel Sequencing (MPS) techniques has been investigated by forensic community aiming introduction of such methods in routine forensic casework analyses. Interesting features presented by MPS include high-throughput, ability to simultaneous genotyping of significant number of samples and forensic markers, workflow automation, among others. Emergence of single nucleotide polymorphism (SNP) as forensic relevant markers was facilitated in this process, since concurrent typing of larger marker sets is necessary for obtaining same levels of individual discrimination provided by other marker categories. In this context, HID Ion Ampliseq Identity Panel is a commercial solution with forensic purposes comprising simultaneous analysis of 90 highly informative autosomal SNPs and 34 Y -chromosome superior clade SNPs for male lineage haplotyping. SNP typing can be obtained with smaller amplicons, and this panel was designed for efficient processing of critical or challenging forensic samples. In this work, a sample of 432 individuals from all five Brazilian geopolitical regions was evaluated with this panel, in order to access feasibility of this panel use in a national basis. Results obtained for all five regions, including forensic parameters, show that this marker set can be efficiently employed for Brazilian nationals in human identification or kinship determination applications, due to high levels of genetic discriminative information content displayed by Brazilians. Interpopulation comparison studies were executed among Brazilian regional populations and 26 worldwide populations, in order to access genetic stratification occurrence. Some levels of population structure were identified, and impact on database design was discussed. Y-chromosome haplotyping of Brazilian samples revealed high levels of European ancestry in Brazilian male lineages, and utility of haplotyping in real forensic casework is addressed. Finally, genotyping and sequencing efficiency with this panel were addressed, as an effort to appraise the adequacy of this panel use in Brazilian national forensic demands.

13-loci STR multiplex system for Brazilian seized samples of marijuana: individualization and origin differentiation.

It is known that Cannabis in Brazil could either originate from Paraguay or be cultivated in Brazil. While consumer markets in the North and Northeast regions are maintained by national production, the rest of the country is supplied with Cannabis from Paraguay. However, the Brazilian Federal Police (BFP) has exponentially increased the seizure number of Cannabis seeds sent by mail. For this reason, the aim of the study was to assess the 13-loci short tandem repeat (STR) multiplex system proposed by Houston et al. (2015) to evaluate the power of such markers in individualization and origin differentiation of Cannabis sativa samples seized in Brazil by the BFP. To do so, 72 Cannabis samples seized in Brazil by BFP were analyzed. The principal coordinate analysis (PCoA) and probability identity (PI) analysis were computed. Additionally, the Cannabis samples' genotypes were subjected to comparison by Kruskal-Wallis H, followed by a multiple discriminant analysis (MDA). All samples analyzed revealed a distinct genetic profile. PCoA clearly discriminated the seizure sets based on their geographic origin. A combination of seven loci was enough to differentiate samples' genotypes, and the PI for a random sample is approximately one in 50 billion. The Cannabis samples were 100% correct as classified by Kruskal-Wallis H, followed by an MDA. The results of this study demonstrate that the 13-loci STR multiplex system successfully achieved the aim of sample individualization and origin differentiation and suggest that it could be a useful tool to help BFP intelligence in tracing back-trade routes.

Exposure of Drosophila melanogaster to Mancozeb Induces Oxidative Damage and Modulates Nrf2 and HSP70/83.

Mancozeb (MZ), a manganese- and zinc-containing ethylene-bis-dithiocarbamate, is a broad-spectrum fungicide. Harmful effects of this fungicide have been reported in nontarget organisms via a not fully understood mechanism. Drosophila melanogaster has provided remarkable contributions for toxicological studies. This work was aimed at evaluating the biochemical targets and implication of oxidative stress in MZ-mediated toxicity in drosophilas. Exposure of flies for fifteen days to MZ at 5 and 10 mg/mL through the diet impaired locomotor performance and induced fly mortality. In parallel, it caused lipid peroxidation and reactive oxygen species (ROS) formation and Mn overload. MZ inhibited superoxide dismutase and inducted catalase and glutathione S-transferase activities. Nitric oxide and reduced glutathione levels were significantly decreased by MZ. Heat shock proteins (HSP70 and HSP83) and Nrf2 mRNA levels were significantly augmented in MZ-exposed flies. Our study reinforced the use of Drosophila melanogaster as a reliable model for the study of biochemical targets of pesticides, and based on our data, MZ induced oxidative damage and Mn accumulation in a concentration-dependent manner. An adaptative cellular state was inducted by the lower concentration of pesticide, possibly contributing to the slighter damage observed.