The tobacco epidemic represents one of the most significant threats to public health globally, resulting in the death of over 8 million individuals annually [1]. This staggering figure encompasses approximately 1.2 million deaths caused by exposure to second-hand smoke. It is important to emphasize that all forms of tobacco are harmful, and there is no safe level of tobacco exposure [2]. While cigarette smoking stands as the most prevalent form of tobacco use worldwide, other tobacco products, such as waterpipe tobacco, various smokeless tobacco products, cigars, cigarillos, roll-your-own tobacco, pipe tobacco, bidis, and kreteks, also contribute to the epidemic [3].

The World Health Organization (WHO) reports that around 1.1 billion people globally are current cigarette smokers, and this number is anticipated to rise to 1.6 billion by the year 2025 [4]. These statistics highlight the urgent need for comprehensive tobacco control measures to combat this pervasive public health challenge.

Tobacco addiction primarily stems from the presence of nicotine, a major alkaloid found in tobacco [5]. Nicotine has been associated with a range of adverse health effects, including cancer, cardiovascular diseases, and respiratory problems [6]. Furthermore, the detrimental impact of nicotine extends to the male reproductive system and spermatogenesis, leading to male infertility [7]. Non-smokers who are exposed to secondhand smoke increase the seriousness of nicotine exposure [8].

Studies conducted on mice have demonstrated that nicotine induces oxidative stress by reducing glutathione levels and the activity of antioxidant enzymes like catalase and superoxide dismutase [9]. These effects contribute to a decrease in sperm count and the suppression of spermatogenesis, directly impacting male fertility [10]. Additionally, NIC has been found to cause DNA damage in sperm, thereby increasing the risk of birth defects and other reproductive complications in offspring [11]. Moreover, research conducted on animals has suggested that prenatal nicotine exposure can result in reduced testicular size and testosterone levels in male offspring [12]. These findings highlight the potential long-term consequences of nicotine exposure on reproductive health.

Turmeric (Curcuma longa) is indeed a plant belonging to the Zingiberaceae family and has a long history of use in traditional medicine [13]. It has been valued for its various potential health benefits, including blood purification, digestion aid, arthritis treatment, liver protection, and anti-inflammatory properties. The distinct yellow color of turmeric is attributed to the presence of curcumin (CUR), a chemical compound that makes up around 3–4% of the plant [14].

Curcumin, the active component in turmeric, has been the subject of scientific investigation due to its potential therapeutic properties [15]. Research suggests that CUR can alleviate the toxicological effects caused by nicotine and regulate the imbalance between cell survival and cell death [16]. It has shown promise as a potential blocker against nicotine-induced stress [17]. Furthermore, CUR exhibits inhibitory effects on lipid peroxidation, reduces the levels of biochemical marker enzymes, and enhances antioxidant status [15]. In fact, the protective and antioxidant effects of CUR have been reported to surpass those of vitamins E and A [18].

Furthermore, research has shown that CUR may be useful in the treatment of male infertility, particularly in cases of oligospermia and decreasing male sexual hormones [19]. Multiple studies have confirmed that CUR can improve fertility in experimental animals by preventing peroxidative modifications in sperm and testicular membrane, enhancing sperm motility, and reducing spermatozoa abnormalities [[20], [21], [22]]. While CUR has demonstrated these beneficial effects in various studies, it is important to note that nano-formulated curcumin has not investigated yet for the treatment of the fertility disorders.

Polymeric nanoparticles have emerged as a promising strategy for encapsulating biologically active materials that could face limitations in using natural products as therapeutic agents [23]. Several studies have demonstrated the effectiveness of this method in enhancing the functional properties of bioactive compounds [24,25]. Specifically, these nanoparticles have demonstrated the potential to protect active substances from degradation, enhance drug absorption, regulate drug release, and target specific organs with precision [12].

In previous works chitosan/protamine nanoparticles (CPNPs) have been utilized to encapsulate doxorubicin or CUR and the produced formula was tested for its in vitro antitumor activity against breast cancer cells [26,27]. The current study was conducted to analyze the protective effect of CUR loaded in CPNPs to offset the damage induced by nicotine in the reproductive system of male rats.