Evaluation of Spectral Transmission in Lens Tissue of Monosodium Glutamate-Induced Hyperglycemic Male Wistar Rats

Monosodium glutamate (MSG), the sodium salt of glutamic acid, is widely used in processed foods as a flavor enhancer, with daily intakes of 0.3–1.0 g in Western countries (Walker & Lupien, 2000). Studies have shown associations between MSG intake and metabolic disruptions in various populations (He et al., 2008, 2011). Research demonstrates that MSG induces metabolic disruptions, including obesity, hyperglycemia, and oxidative stress in rodents through mechanisms involving hypothalamic lesions, hyperlipidemia, and increased oxidative stress (Kazmi et al., 2017; Zanfirescu et al., 2019). MSG consumption has been linked to increased oxidative stress markers and inflammatory responses in multiple organ systems (El-Bakry et al., 2025; Kesherwani et al., 2024).

The ocular lens is critical for vision but susceptible to oxidative and metabolic stress. Cataracts remain a leading cause of global visual impairment (Bourne et al., 2013). Lens transparency requires both the orderly arrangement of lens cells and the high density and close packing of crystallin proteins (Shiels & Hejtmancik, 2019). In hyperglycemia, elevated blood glucose promotes glycation and aggregation of lens crystallins, reducing transparency and increasing cataract risk (Kumar & Cherian, 1996; Lyons et al., 1991; Swamy et al., 1993). Biochemical changes, particularly protein aggregation and post-translational modifications, impair lens function and contribute to cataract formation (Hains & Truscott, 2010; Truscott & Friedrich, 2019). MSG’s induction of oxidative stress raises concerns about potential lens damage. However, data on MSG’s direct effects on lens transparency in hyperglycemic models remain limited.

We hypothesized that chronic MSG exposure at 750 mg/kg reduces lens spectral transmission in male Wistar rats through hyperglycemia-induced protein aggregation and oxidative damage, potentially increasing cataract risk. This study evaluates spectral transmission in lens homogenates of MSG-induced hyperglycemic rats using UV-Visible spectrophotometry to assess optical changes.

Rats were randomly assigned to two groups (n = 5 each) using a computer-generated random number table: Control group received distilled water orally while experimental group received MSG (Aji-no-moto, 99% purity) at 750 mg/kg body weight daily via oral gavage for 28 days. The MSG dose was selected based on studies showing metabolic effects in rodents, equivalent to high human dietary exposure (Sharma et al., 2013; Rahimi Anbarkeh et al., 2019). Body weight was measured weekly during acclimatization and on alternate days during treatment using a 500 g mechanical scale. Blood glucose was monitored using a glucometer and test strips.

Animals and Housing

Ten healthy male Wistar rats (80–100 g) were sourced from a certified animal farm in Ogbomosho, Oyo State, Nigeria, and housed in the Physiology Laboratory at the University of Ilorin under standard conditions (22 ± 2°C, 12-hour light/dark cycle). Rats had ad libitum access to grower mash and distilled water during a 7-day acclimatization period. Procedures were approved by the University of Ilorin Ethics Committee (approval no. UIL/ERC/2023/012) and adhered to the National Research Council’s Guide for the Care and Use of Laboratory Animals (2011) and the 3Rs principle (Replacement, Reduction, Refinement).

MSG Preparation and Administration

MSG (15 g) was dissolved in 19.8 ml distilled water daily to prepare a fresh stock solution (He et al., 2008). The experimental group received 750 mg/kg MSG via oral gavage, while controls received an equivalent volume of distilled water.

Euthanasia and Lens Extraction

On day 36, after overnight fasting, rats were anaesthetized with intraperitoneal ketamine (50 mg/kg) and euthanized by cervical dislocation by trained personnel (National Research Council, 2011). Eyes were enucleated, and lenses were dissected via a posterior approach, rinsed in cold phosphate-buffered saline (PBS, 0.01 M, pH 7.4), and fixed in 10% phosphate-buffered formalin (Li et al., 2014).

Lens Homogenate Preparation

Lenses were homogenized in 180 μL cold PBS at 4°C using a dounce homogenizer. Homogenates were centrifuged at 10,000 × g for 10 minutes at 4°C, and supernatants were stored at −20°C until analysis (Donaldson et al., 2001).

UV-Visible Spectrophotometry

Lens homogenates were analyzed using a double-beam UV-Visible spectrophotometer (Analytik Jena) scanning from 250 to 700 nm. Parameters included scan speed (10.0 nm/s), integration time (0.1 s), measurement interval (1.00 nm), and lamp change wavelength (320 nm). A PBS-filled cuvette served as the blank, and the spectrophotometer was calibrated before each run. Three replicates per sample were analyzed, and absorbance/transmittance spectra were recorded to assess lens clarity (Hejtmancik & Shiels, 2015).

Statistical Analysis

Data normality was confirmed using the Shapiro-Wilk test. Unpaired t-tests compared body weight, blood glucose, and lens transmittance between groups, with significance set at p < 0.05. Analysis of variance (ANOVA) assessed effect sizes (eta-squared, η²). Analyses were performed using GraphPad Prism (version 9.0). Results were visualized using tables and graphs. A power analysis justified the sample size (n = 5 per group) to detect a 20% difference in transmittance with 80% power (α = 0.05).

Ethical Considerations

All experimental procedures involving Wistar rats were conducted in strict accordance with the principles of the National Code of Health Research Ethics of Nigeria and the ARRIVE (Animal Research: Reporting of In Vivo Experiments) guidelines. Efforts were made to minimize animal suffering, including appropriate housing, handling, and humane endpoints.

Chronic monosodium glutamate (MSG) administration at 750 mg/kg for 28 days induced significant metabolic changes in male Wistar rats, including weight gain and hyperglycemia (p < 0.05), consistent with prior reports demonstrating that MSG consumption is associated with metabolic dysregulation in both animal models and human populations (He et al., 2008, 2011; Kazmi et al., 2017). The observed reduction in lens transmittance (p = 0.053) and increased absorbance (p = 0.145) suggest protein aggregation, likely due to hyperglycemia-induced glycation and oxidative stress, processes known to impair lens clarity through accumulation of covalent modifications including deamidation, oxidation, and glycation that destabilize crystallin proteins (Hains & Truscott, 2010; Kumar & Cherian, 1996; Truscott & Friedrich, 2019). MSG administration has been demonstrated to elevate oxidative stress markers, increase lipid peroxidation, and induce inflammatory responses in multiple organ systems (El-Bakry et al., 2025; Kesherwani et al., 2024), which may contribute to reactive oxygen species (ROS) generation that oxidizes lens crystallins and reduces transparency.

The lens transparency depends on maintaining native tertiary structures and high solubility of crystallin proteins, and protein aggregation is the primary cause of cataract, the leading cause of blindness worldwide (Shiels & Hejtmancik, 2019). In diabetic and hyperglycemic conditions, elevated glucose promotes non-enzymatic glycation of lens crystallins, leading to the formation of advanced glycation end products (AGEs) that induce protein cross-linking, aggregation, and loss of transparency (Kumar & Cherian, 1996; Lyons et al., 1991; Swamy et al., 1993). Our findings of reduced transmittance align with established mechanisms of cataract formation wherein oxidative damage, glycation, and other post-translational modifications lead to partially unfolded, aggregation-prone crystallin intermediates that form insoluble, light-scattering aggregates (Hains & Truscott, 2010; Truscott & Friedrich, 2019).

These findings suggest a potential link between MSG exposure and lens opacity in rats, but human implications require cautious interpretation. MSG has been shown to induce metabolic and oxidative stress in animal models (El-Bakry et al., 2025; Kesherwani et al., 2024), and given cataracts’ substantial global burden as a leading cause of vision loss (Bourne et al., 2013), dietary MSG may pose a risk for individuals predisposed to hyperglycemia. However, the relationship between MSG consumption and metabolic outcomes in human populations remains controversial, with some studies finding associations with overweight (He et al., 2008, 2011) while comprehensive reviews note the need for careful evaluation of safety evidence (Kazmi et al., 2017; Zanfirescu et al., 2019). Furthermore, causality cannot be inferred from this study alone, as the rodent model, dose administered (750 mg/kg), and duration of exposure may not directly translate to human dietary consumption patterns.

In summary, chronic MSG exposure induces metabolic stress and may impair lens clarity in rats through mechanisms involving hyperglycemia, oxidative stress, and protein aggregation, suggesting a potential association with cataract risk. The progression from initial glycation events to the formation of high-molecular-weight crystallin aggregates, as documented in diabetic cataract models (Lyons et al., 1991; Swamy et al., 1993), provides a mechanistic framework for understanding how MSG-induced hyperglycemia could contribute to lens damage. These findings highlight the need for further research on MSG’s ocular safety in humans, particularly longitudinal studies examining lens health in populations with varying levels of MSG consumption and in individuals with pre-existing metabolic conditions that may increase vulnerability to lens damage.